St. Gallen early breast cancer management recommendations are becoming more applicable to most countries even with different levels of income and healthcare scenarios, Egypt as an example

St. Gallen early breast cancer management recommendations are becoming more applicable to most countries even with different levels of income and healthcare scenarios, Egypt as an example | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article St. Gallen early breast cancer management recommendations are becoming more applicable to most countries even with different levels of income and healthcare scenarios, Egypt as an example Hussein Khaled, Yousry Wasef Nada, Kareem Mohamed Ramadan, Shawkat Fekry, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4251493/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Purpose: One of the most important meetings in the field of developing clinical guidelines for early management for breast cancer is the 18 th St. Gallen International Breast Cancer Conference that was held in March 2023. To tailor these guidelines to suit clinical practice of oncologists in Egypt, an Egyptian Panel were asked to vote on most of the questions of the original St. Gallen consensus. Methods : The panel consisted of 76 different oncology specialists. 100 questions were assembled and then projected on the monkey survey website. The answers were analyzed in relation to the answers of the St. Gallen panel, 2023. Results and conclusions : A consensus (≥ 50% approval) among Egyptian panel was reached in answering 71/100 questions denoting the need of more research tackling different problems in taking care of patients having early breast cancer. Comparing answers of both St. Gallen and Egyptian panel to common questions, no consensus was only in 9 out of the 100 questions. So, St. Gallen recommendations are becoming more and more applicable to most countries even with different levels of income and healthcare scenarios. Breast cancer Adjuvant therapy Egypt Figures Figure 1 Introduction The 18th St. Gallen Consensus Conference on early breast cancer treatment was held in Vienna in March 2023. On the last day of the meeting, the 70 members of the panel discussed and voted on recent clinical research findings focusing on diagnosis, and therapy guidelines aiming to optimize early breast cancer patient diagnosis and treatment ( 1 ). Subsequently, and as was done previously ( 2 , 3 ), a monkey survey vote was arranged to vote on some of the controversial issues of early breast cancer management that are more relevant to Egyptian patients. Methods A steering committee prepared survey questions that were adapted from the 18th St. Gallen ( 4 ), with some adaptation to suit the Egyptian situation. Then, the prepared questions were delivered online through the monkey survey website: https://www.Surveymonkey.Com . The survey was formed of 100 questions, and the answers were reported in percentages. A blank box was included with every question so the voter may express any additional comment(s) or explain in more detail her/his answer. After 3 weeks of online projection, the answers and data were collected and analyzed by the steering committee in preparation for writing the manuscript, which was then distributed and shared by the whole group for any further comments. Results The detailed questions and answers of the voting results of the E-panel as well as graphic projections of a detailed comparison between the original St Gallen answers ( 4 ) vs. the Egyptian voting results for the same shared questions are shown in the supplement 1. Supplement 2 illustrates and summarizes Egyptian panel (E-panel) voting for questions where the results were either recommend (≥ 50%) or strongly recommend (≥ 75%). It also compares voting results between E-panel and St Gallen panel (S-panel). The following text will illustrate only items that gained endorsement of the E-panel by > 50% of voters. General Practice Issues While 95% of E-panel expressed situations where drug costs prevent some patients from receiving important therapies, only 43% of S-panel positively reported on this issue. Most developing countries, in some European countries, and even in certain areas in the US authorities are facing this situation. ASCO has been discussing this problem focusing on equity of care. They have done a lot in terms of supporting the states for drug repository programs. Also, some US societies have put forward programs to find a way to repurpose those drugs ( 5 ). In addition, one way to solve this problem is to bring people together, so having members of the government, from industry, physicians to discuss prices and strict guideline applications is also important, so that physicians would not be caught in the middle and don’t have the resources to maintain their practices. Burnout was also discussed. Thirty-seven percent an additional panel reported burnout themselves, and additional 38% consider burnout of a significant concern for many colleagues. These percentages were reported to be 12%, and 79%, respectively for the S-panel. In the opinion of E-voters, the causes of burnout were either because of inadequate healthcare systems (45%), or due to excessive clinical load (32%). The same was expressed by the S-voters, being 60% and 12%, respectively. Then attention was directed to breast cancer survivors’ well-being. On asking “in patients with body mass index (BMI) of more than 25, is there a specific diet that can lower the risk of breast cancer recurrence?”. The S-panel was not convinced by (No 73%), while there was no consensus between members of the E-panel (48% Yes, and 34% No), but by a clear majority (83% and 81%, respectively) both panels voted that keeping lower BMI is of general value as suggested by a meta-analysis recently published ( 6 ). The S-panel (70%) voted to recommend acupuncture to alleviate arthralgia caused by aromatase inhibitor treatment or neuropathy induced by chemotherapy. On the contrary, the E-panel voted against its routine use (63%). A case of a young patient treated by tamoxifen / ovarian function suppression as an adjuvant therapy for patients with 4 or more involved axillary lymph nodes and she wants to get pregnant was presented. The panels were asked if it is possible to interrupt endocrine therapy after 2 years in view of IBCSG / BIG / Alliance POSITIVE trial data ( 7 ). Seventy-nine percent of the S-panel and 56% of the E-panel would not encourage her getting pregnant. This voting recommendation would be since the POSITIVE trial included only very few patients with ≥ 4 involved axillary nodes. In response to a question whether postmenopausal women on AI treatment for ER positive breast cancer should not be offered intravaginal estrogens because of concerns over systemic estrogen exposure and impact of adjuvant treatment efficacy, 58% of S-panel did not agree, while 56% of E-panel agree on this advice. Pathology Both panels were not convinced that stromal tumor-infiltrating lymphocytes (TILs) routine testing is to be used to assess breast cancer risk of recurrence. They voted by a clear majority to give adjuvant chemotherapy to 2 early breast cancer case examples; the first case was 43 old women that has undergone lumpectomy for 1.6 cm, node-negative, grade3, triple negative breast cancer (TNBC). TILs were 75%. The second case has undergone surgery for stageT1b TNBC, for a tumor measuring 0.8 cm, and had a high TILs > 50%. On another issue, both panels voted (> 90%) that breast cancer patients should have access to genetic counselors. Also, and as shown in Table 1 , the panels were discussing risk-reducing measures with a woman who has been diagnosed with early stage breast cancer. They were asked if they would preferentially recommend either risk-reducing surgery, or intensive (mammogram and MRI-based) screening for both pre- and post-menopausal women with BRCA1, BRCA2, PALB2, ATM, and CHEK2 mutations. Most of the E-panel (> 50%) preferred intensive screening for all subtypes except pre-menopausal women with either BRCA1 or BRCA2 mutations where they preferred doing risk-reducing surgery. On the other hand, the S-panel preferred surgery both pre- and post-menopausal women with BRCA1, and BRCA2 mutations. They also preferred surgery by a narrow vote (42% vs 32%) for pre-menopausal women with PALB2 mutations. Table 1. Types of risk-reducing measures with a woman with early stage breast cancer Topic (Question no.) Choice E-panel recommendation S-panel recommendation Consensus between E-panel and S-panel (Qs:16-25) : You are discussing risk-reducing mastectomy and intensified surveillance with a woman who has been diagnosed with early stage breast cancer. She has had genetic testing and harbors a deleterious mutation. As part of a shared decision making process, she asks your opinion on management. Indicate if you would preferentially recommend either contralateral risk-reducing surgery, or intensive (mammogram and MRI-based) screening, or no preference (either) if she is Genetic mutation and menopausal status Choice Surgery Intensive screening Surgery Intensive screening premenopausal with BRCA1 mutation 55% 40% 67% 13% consensus postmenopausal with BRCA1 mutation 41% 53% 61% 17% No consensus premenopausal with BRCA2 mutation 50% 47% 63% 14% consensus postmenopausal with BRCA2 mutation 33% 57% 42% 32% No consensus premenopausal with PALB2 mutation 30% 53% 42% 32% No consensus postmenopausal with PALB2 mutation 23% 57% 20% 53% consensus premenopausal with ATM mutation 20% 57% 9% 73% consensus postmenopausal with ATM mutation 22% 57% 1% 79% consensus premenopausal with CHEK2 mutation 22% 58% 8% 71% consensus Postmenopausal with CHEK2 mutation 20% 60% 1% 79% consensus DCIS Both the E-panel and the S-panel recommended radiation therapy for a woman being either pre- or post-menopausal that has undergone breast conserving surgery for DCIS and this DCIS is grade 1 to 2, without comedo necrosis, and 70 years and having tumors < 2 cm with or without comedo necrosis. For women aged 65 years or less, both panels agreed to give radiation therapy if the tumor is < 2 cm with or without comedo necrosis, and recommendations were stronger if patients’ age was < 50 years. Table 2 Indications of radiotherapy in cases of DCIS Topic (Question no.) Egyptian Consensus S-panel recommendation Consensus between E-panel and S-panel Recommend* Strongly recommend* A healthy woman has undergone breast conserving surgery for DCIS. This DCIS is grade 1 to 2, without comedo necrosis, and less than 2 cm in diameter. Being premenopausal, should she receive radiation therapy? (Q26) Yes (64%) Yes (72%) consensus between both panels If the above woman is postmenopausal? (Q27) Yes (54%) Yes (72%) consensus between both panels If the above woman is premenopausal and being ER + will take endocrine therapy? (Q28) Yes (66%) Yes (62%) consensus between both panels Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age above 70, DCIS smaller than 2 cm: would you give radiation therapy? (Q31). No (52%) No (66%) consensus between both panels Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age above 70, DCIS smaller than 1 cm: would you give radiation therapy? (Q32). No (64%) No (66%) consensus between both panels Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age above 70, DCIS without comedonecrosis: would you give radiation therapy? (Q33). No (63%) No (55%) consensus between both panels Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age above 70, DCIS smaller than 2 cm without comedonecrosis: would you give radiation therapy? (Q34). No (59%) No (73%) consensus between both panels Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age 50–65, DCIS smaller than 2 cm: would you give radiation therapy? (Q35). Yes (75%) Yes (50%) consensus between both panels Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age 50–65, DCIS smaller than 1 cm: would you give radiation therapy? (Q36). Yes (55%) Yes (50%) consensus between both panels Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age 50–65, DCIS without comedonecrosis : would you give radiation therapy? (Q37). Yes (52%) Yes (66%) consensus between both panels Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age 50–65, DCIS smaller than 2 cm without comedonecrosis : would you give radiation therapy? (Q38). Yes (54%) Yes (42%) No (38%) No consensus among members of S-panel Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age below 50, DCIS smaller than 1 cm : would you give radiation therapy? (Q39). Yes (73%) Yes (61%) consensus between both panels Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age below 50, DCIS smaller than 2 cm : would you give radiation therapy? (Q40). Yes (55%) Yes (61%) consensus between both panels Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age below 50, DCIS without comedonecrosis: would you give radiation therapy? (Q41). Yes (66%) Yes (75%) consensus between both panels Patients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age below 50, DCIS, smaller than 2cm without comedonecrosis: would you give radiation therapy? (Q42). Yes (66%) Yes (60%) consensus between both panels Surgery In case of a patient who has undergone neoadjuvant treatment with AC/T chemotherapy regimen, with a significant clinical response, and at surgery, there is residual disease in the axilla. The tumor is triple negative with nodal burden macrometastasis in 1 of 3 SLN. Panelists were asked if they would recommend completion of axillary dissection or axillary radiation. E-panel recommended axillary lymph node dissection by 55%, while S-panel voted for the same choice by 47%. Another case was exhibited as “A 63 year old woman was treated 9 years ago for a stage 2 node-negative breast cancer with lumpectomy and radiation therapy, as well as adjuvant systemic endocrine therapy that stopped 2 years ago. Now she has had ipsilateral tumor recurrence. No more than grade 1 or only very localized grade 2 side effects at the level of the skin and/or the soft tissues are present. The tumor is ER+/Her2-. Staging scans are negative. The lesion is less than 2 cm in size, 3 cm from nipple, and would be amenable to breast conserving surgery with acceptable aesthetic results” Both panels recommended doing mastectomy (59% and 74% votes of E- and S-panels, respectively). Another patient was discussed. While she was receiving adjuvant aromatase inhibitor, developed isolated local recurrence. Her disease was strongly + ve ER and -ve HER2. Her local recurrence was fully excised. The patient did not receive adjuvant chemotherapy. When asked about further management, both panels recommended adjuvant chemotherapy (54%, and 63% of E- and S-panels respectively). Radiation therapy Both panels endorsed (> 65%) moderate hypofractionation as the preferred radiation schedule for chest wall irradiation irrespective of nodal irradiation after mastectomy, after breast conserving surgery for invasive cancer, and by > 55% after breast conserving surgy for DCIS. Also, both panels agreed that for routine radiation therapy for early breast cancer, there is at present no clinical advantage to proton therapy over photon therapy (> 65%). A boost dose of radiation therapy to the primary tumor bed after breast conserving surgery was approved and indicated by 50% of the E-panel in patients with at least 1 of the 4 following prognostic factors: high grade cancers, extensive intraductal component, TNBC or HER2- positive subtypes, and age below 50 years. However, no consensus was reached among members of S-panel regarding the number of prognostic factors needed to give a boost dose. While 63% of the S-panel agree on the most important clinical observation from the PRIME-II that radiation lowers in-breast recurrence and therefore is effective, only 54% of the E-panel endorsed this statement. Then both panels were asked a series of questions on the role of post mastectomy radiation therapy in relation to both tumor size (T2, and T3), and to its biologic subtype (ER + ve, HER2 + ve, and TNBC). As shown in Fig. 1. It is obvious that with increasing disease burden the percentage of recommending post mastectomy goes up specially for HER2 + and TN tumors. The Egyptian survey did not include some questions on higher tumor burden when it was clear that voters recommend post mastectomy radiotherapy in lower earlier tumor stages. The S-panel did not recommend radiation in case of deleterious ATM gene mutation, while the E-panel split in their answers (29% yes, 32% no, and 39% abstain). Adjuvant endocrine therapy in premenopausal patients Fifty percent of E-panel recommended tamoxifen and OFS while 31% of S-panel advised AI and OFS for IDC G2 (T1 N0) with low recurrence score. Published data of SOFT and TEXT trials, showed a DFS of 92.8% in the exemestane plus ovarian suppression group, compared to 88.8% in the tamoxifen/ovarian suppression group (HR for recurrence, 0.66; 95% CI, 0.55–0.80; P < .001). On the other hand, OS data was not significantly different between both groups (HR for death in the exemestane plus ovarian suppression group, 1.14; 95% CI, 0.86–1.51; P = .37). The NCCN guidelines included an aromatase inhibitor/ovarian suppression for 5 years as an adjuvant endocrine therapy option for premenopausal patients with HR positive cases at higher risk of recurrence e.g., young age, high-grade tumor, and lymph-node involvement ( 8 , 9 ) For assessing functional menopause in a patient who is 38 years of age and is amenorrheic and experiencing menopausal symptoms while receiving GnRH agonist and AI therapy, 44% of S-panel voted for semiannual monitoring of estradiol levels vs. 37.5% in E-panel. However, 37% of S-panel considered no additional test vs. 21% of E-panel. Ovarian function suppression induces amenorrhea and reduces ovarian estrogen synthesis without causing permanent menopause, so menopausal status in those receiving ovarian function suppression cannot be determined. Thus standard criteria for the diagnosis of menopause in patients with breast cancer are lacking ( 10 ). It was also recommended by a clear majority of both St. Gallen (65%) and Egyptian (63%) panels to give monthly GnRH agonist in any premenopausal patient that has had breakthrough menstrual bleeding while receiving GnRH every 12 weeks. Regarding extended endocrine therapy for patient with stage 3 breast cancer that has received 5 years of AI plus ovarian suppression, and she has had substantial arthralgia but otherwise found treatment to be acceptable, the higher percentage of voting in St. Gallen (35%) was for continuation with tamoxifen while 23% of the Egyptian side voted for discontinuation of therapy. Adjuvant endocrine therapy is recommended for a minimum of 5 years. A retrospective analysis by Oxford University studied risk of recurrence for years 5 through 20 after 5 years of endocrine therapy. These data showed a considerable risk of recurrence between years 5 and 20 in these patients treated with initial 5 years of endocrine therapy. Data has now emerged showing benefit of extended endocrine therapy in improving DFS ( 11 ). The NCCN Guidelines for Breast Cancer recommend 5 years of tamoxifen with or without ovarian suppression (category 1) or ovarian suppression plus an aromatase inhibitor for 5 years (category 1). Adjuvant therapy in postmenopausal patients There was a great difference between the two panels when asked about doing a genomic signature assay for a patient with luminal breast cancer grade 2 T1b N0, as 74% of S-panel voted for not doing the assay, while 53% of the E-panel voted for doing it. For patients with invasive ductal or lobular tumors greater than 0.5 cm in diameter and lymph node-negative patients, the NCCN recommendation is strongly considering the 21-gene RT-PCR assay to help estimate likelihood of recurrence and benefit from chemotherapy. An exploratory analysis from the TAILORx study, showed that adjuvant chemotherapy may be considered in patients 50 years of age or younger with a 21-gene RS of 16–25. Also, patients with T1b tumors with low grade histology should be considered for endocrine monotherapy, as the TAILORx study did not include patients with such tumors ( 12 ). Neo/adjuvant chemotherapy There was also a discordance between the two panels as regard prescribing adjuvant chemotherapy for a 57 year old patient who has grade 2 luminal breast cancer (T1b N0) with high genomic risk by MammaPrint assay as 69% of S-panel did not recommend adjuvant chemotherapy while 75% of the E-panel recommended chemotherapy. For the same case but assuming that tumor size was T2N0 instead of T1No, both panels agreed by a clear majority (78% and 86%, respectively) to give adjuvant chemotherapy. Considering recommending adjuvant chemotherapy for the same case criteria but detailing the decision based on tumor size, a sum of 56% of S-panel agreed to give adjuvant chemotherapy if tumor size was 1 cm or more, and 22% voted for not giving chemotherapy for stage I tumor like this. On the other hand, 55% of the E-panel voted for giving chemotherapy regardless of tumor size. Results from the randomized MINDACT trial, demonstrated that among patients at low clinical risk/ high genomic risk, 5-year survival with no distant metastasis was 95.8% with chemotherapy (95% CI, 92.9 to 97.6), compared with a rate of 95.0% (95% CI, 91.8 to 97.0%) without chemotherapy (adjusted HR for distant metastasis or death with chemotherapy vs. no chemotherapy,1.17; 95% CI, 0.59 to 2.28). These data suggest that the results of the 70-gene signature do not provide evidence for making recommendations regarding chemotherapy for patients at low clinical risk ( 13 ). In case of a postmenopausal patient that has had IDC, G1, luminal A, ki 67 < 15%, and low recurrence score, 6%,14%, and 62% of S-panel while 21%,14%, and 39% of E-panel voted for 2, 3, and 4 positive lymph nodes, respectively as the number of positive axillary lymph nodes that would prompt recommending adjuvant chemotherapy. It is worth mentioning that for patients with four or more involved nodes, the NCCN guidelines recommends systemic adjuvant chemotherapy followed by endocrine therapy. While a secondary analysis of the prospective SWOG 1118 trial demonstrated no benefit for chemotherapy for patients with 1–3 involved ipsilateral axillary lymph nodes and a low RS, there was benefit for the addition of adjuvant chemotherapy in those with high-RS (≥ 31) from the 21-gene assay ( 14 ). In the MINDACT trial, among patients with 1–3 positive nodes who had a high clinical risk of recurrence but low risk by the 70-gene assay, the rates of survival were similar between those who received adjuvant chemotherapy in addition to adjuvant endocrine therapy versus those received adjuvant endocrine therapy alone, suggesting that chemotherapy could be omitted in this group ( 13 ). In case of invasive lobular carcinoma without pleomorphism, luminal A, stage 1–3, grade 1–2, 60% of S-panel recommended giving neo/adjuvant chemotherapy, but the Egyptian team was divided between supporters and opponents of neo/adjuvant chemotherapy for such a case. Data showed that ILC had poor response to chemotherapy leading to lower OS rates following NAC compared to those observed in IDC ( 15 ). In part, this was explained by the less frequent pCR occurring in ILC subset. An analysis of a large set of data comprising two NAC trials that have included 676 patients showed that 75% of cases had ILC ( 16 ). Following neoadjuvant chemotherapy, pCR rates were significantly less likely to be achieved in ILC than hallmark in IDCs cases (11% versus 25%). ILC poor chemo-sensitivity could be explained by its different biological characteristics. These characteristics include low grade, low mutational burden, ER positivity, and a low rate of proliferation assessed with Ki-67 ( 17 ). After addition of low genomic signature score to the previous case, 63% of ST Gallen changed voting and agreed not to give neo/adjuvant chemotherapy, while the E-panel was still confused between the two opinions. Comparing the use of endocrine plus chemotherapy vs. endocrine therapy alone in patients with ILC ( 18 ), no survival difference was observed between both arms. Also, Oncotype Dx testing in ILC patients revealed that most cases would receive little benefit from chemotherapy. With more data, gene signatures assays may prove to be a vital tool in choosing chemotherapy for ILC patients ( 19 ). Triple Negative Therapy Both Egyptian and S-panel agreed by a similar percentage (78%) that carboplatin-containing regimen should be included given to patients receiving neoadjuvant therapy for stage 2 or 3 TBC who are also receiving taxane, anthracycline, and cyclophosphamide based chemotherapy, even when pembrolizumab is being administered. Dose density is associated with improved EFS and OS benefits in anthracycline- and taxane-based regimens. The KEYNOTE-522 regimen (which included pembrolizumab) did not include dose-dense AC, and thus the benefits observed with this regimen, are independent of dose density. There are practical considerations of substituting an every-2-week AC with an every-3-week regimen. But this would increase the complexity of the regimen, in terms of not only additional visits but also uncertainty regarding duration of pembrolizumab, because AC would finish several weeks earlier. Although studies evaluating dose density suggest acceptable toxicity profiles compared with non–dose-dense chemotherapy, the toxicity and feasibility of dose density after 3 months of carboplatin and paclitaxel with pembrolizumab is unknown ( 20 ). For these reasons, 46% of E-panel and 38% of S-panel were unsure about replacing 3-week approach with dose dense one. Advising adjuvant pembrolizumab after achieving pCR in the above example was also discussed. Although the two panels agreed to continue adjuvant pembrolizumab after pCR (59% and 66% of the E- and S-panels, respectively), there was a considerable percentage (32%) that couldn’t be neglected in S-panel who preferred to not to give the drug. The lower percentage of the E-panel may be explained by the affordability of the drug due to its high cost. In the KEYNOTE trial, EFS benefit in those achieving pCR was almost identical between the control and experimental arms (92.5% vs 94.4%, respectively). This analysis was exploratory and was not powered to make a definitive conclusion. However, this should be considered in the context of the wealth of data demonstrating the association of pCR with high EFS rates for individuals achieving pCR. Furthermore, although most of the toxicity of the KEYNOTE-522 regimen was seen in the neoadjuvant portion of treatment, the toxicity of single-agent pembrolizumab given in the adjuvant sitting was not negligible ( 21 ). Given the unclear benefit of adjuvant pembrolizumab in those achieving pCR, and the demonstrated toxicity in the adjuvant phase of treatment, clinicians may discuss potential benefits versus toxicity with individuals to determine whether to continue adjuvant pembrolizumab. The preferred approach for a 60 year old female patient with TNBC having T2N0 disease was neoadjuvant chemotherapy and pembrolizumab in 65% of S-panel and 46% in E-panel. Thirty percent 30% of E-panel voted for neoadjuvant chemotherapy only vs. 22% in S-panel. The KEYNOTE-522 results need to be considered in the context of its toxicity; a 77.1% high-grade treatment-related adverse events rate is very high, and ideally alternative less toxic treatment regimens should be considered, especially in patients in whom the benefit of pembrolizumab is less clear. Subgroup analysis, albeit exploratory and with relatively small numbers, demonstrated less apparent benefit in those with a performance status of 1 and in older patients ( 22 ). So standard dose-dense AC/paclitaxel may be considered in older patients and/or those with a performance status > 0, especially those with node-negative disease. Approximately the same percent in both panels (~ 42%) agreed to do primary surgery for stage 1 TNBC that clinically have no indication for neoadjuvant treatment, while 46% in S-panel and 25% in E-panel recommended ‘chemotherapy only’ as an appropriate neoadjuvant therapy for small TNBC tumors. pCR to preoperative systemic therapy is associated with an extremely favorable DFS and OS rates, particularly in situations in which all treatment is given preoperatively. These correlations are strongest for TNBC, somewhat less so for HER2-positive disease, and least for ER-positive disease ( 23 ). According to NCCN guidelines, preoperative systemic therapy is preferred for TNBC, if ≥ cT2 or ≥ cN1 and preoperative systemic therapy can be considered for cT1c, cN0 TNBC. The KEYNOTE-522 study enrolled patients with stage II or III TNBC, and therefore, any patient meeting these criteria should be considered for chemotherapy and pembrolizumab ( 21 ). The panels were asked if it is indicated to give adjuvant pembrolizumab in addition to standard chemotherapy for triple negative breast cancer patient who was treated with primary surgery and had positive lymph node. Most of S-panel (62%) were against this approach while 46% in E-panel agreed to give adjuvant pembrolizumab as well. Based on NCCN guidelines, adjuvant pembrolizumab is recommended only if pembrolizumab-containing regimen was given preoperatively ( 10 ). Another adjuvant consideration in patients with residual disease concerns those with germline BRCA mutations. Addition of olaprib to pembrolizumab in adjuvant setting was suggested by 62% of ST Gallen panel but the Egyptian panel, 32% preferred to give the drugs in sequence. Although adjuvant XXXlaparib was not part of the KEYNOTE-522 protocol, the addition of adjuvant XXXlaparib in patients with residual disease and a germline BRCA mutation is an attractive consideration because it targets a different pathway. The combination of XXXlaparib and pembrolizumab has been studied, and toxicities described are consistent with the profile of the individual drug ( 24 ). Thus, administration of XXXlaparib, along with standard pembrolizumab, is reasonable in patients with germline BRCA mutations and residual disease after the KEYNOTE-522 regimen. Her2 Positive The preferred adjuvant treatment for a casewith stage 1, HER2 positive tumor is TH (Paclitaxel, trastuzumab) as suggested by 85% of S-panel. Forty-two percent of E-panel preferred TH (Paclitaxel, trastuzumab) while 46% voted for TCHP (Docetaxel, carboplatin, trastuzumab, pertuzumab) The NCCN guidelines has included paclitaxel and trastuzumab as an option for patients with low-risk, HER2-positive, stage 1 tumors. This is based on a trial that studied this combination in 406 patients with small, node negative, HER2 positive tumors. The results showed that the 3-year DFS rate was 98.7% (95% CI, 97.6–99.8) and the risk of serious toxic effects with this regimen was low with 0.5% incidence of heart failure ( 25 ). The appropriate adjuvant regimen for patients presenting clinically with node negative disease, and who have received TCHP neoadjuvant therapy, and achieved a pCR is trastuzumab as recommended by 63% of S-panel vs. 57% of E-panel. The same percent in both panels (33%) advised for adjuvant Trastuzumab and pertuzumab. Kim et al., found that patients who have received neoadjuvant chemotherapy with dual HER2-blockade, and achieved pCR had an excellent 3-year RFS and results did not differ according to the type of adjuvant anti-HER2 therapy (TP vs T)being 91.7% in TP and 94.2% in T ( 26 ). Both panels accepted (57% each) to give adjuvant trastuzumab emtansine to a patient with HER positive breast cancer that has received TCHP neoadjuvant therapy, and at surgery there was residual disease that is HER2 negative. Using platinum-based treatment for all patients with BRCA1 or BRCA2 mutations who receives neo/adjuvant chemotherapy is accepted by 64% of Egyptian panel and 38% only of ST Gallen panel. Several studies have shown improved pCR rates with incorporation of platinum. However, long-term outcomes remain unknown. So, the routine use of platinum agents as part of neoadjuvant therapy for TNBC is not recommended for most patients, but it may be considered in select patients such as those for whom achieving better local control is necessary. In addition, if platinum agents are included in an anthracycline-based regimen, the optimal sequence of chemotherapy and choice of taxane agent is not established ( 27 ). Oligometastatic Disease Both panels agreed to recommend definitive breast surgery and radiation therapy (E-panel 70%, and S-panel 68%) for a case that had ER-/Her2 + tumor, and staging scans revealed a 4 cm tumor, positive axillary, a single pulmonary nodule and she achieved clinical CR with induction THP. In another patient having stage 2 breast cancer on one side and an isolated contralateral axillary lymph node, the majority of the two panels (84% and 75% of the E- and S-panels, respectively) recommended definitive therapy with curative intent including contralateral axillary surgery and radiation therapy, and adjuvant treatment as standard. Male breast cancer Tamoxifen was endorsed by both panels to be the preferred adjuvant endocrine therapy option for men with breast cancer (Stage 1 excluding minimal risk), ER + HER2 breast cancer (63% and 80% of the E- and S-panels, respectively). However, these percentages dropped to 39%, and 51% for men with stage 3, ER + HER2- breast cancer. Discussion Among the Egyptian panel, a consensus (≥ 50% approval) was reached in answering 71 out of the 100 questions projected to the panelists. When comparing the answers to these questions by both the E- and the S-panel, was a consensus in answering 82 questions (82%), and no consensus in answering 9 questions. It was difficult to compare answers of the remaining 9 queries since there was no consensus among members of the S-panel themselves. So, contrary to the S-panel, E-panel did not recommend using aquapuncture to alleviate symptoms of arthralgia, or neuropathy for patients receiving AI or chemotherapy. They also did not agree to recommend palliative intravaginal estrogens to be given to postmenopausal women. On the other hand, Egyptian panelists recommended postoperative radiotherapy for patients who have undergone radical mastectomy for T2 lesions whether they are ER + ve with cancer in one lymph node, or Her2 + ve with positive micro or macro metastases in one lymph node, and in TNBC even with micro metastases in one axillary node. The S-panel did not recommend giving postoperative radiotherapy to these patients. Also, the E-panel recommended asking for a genomic signature assay for a postmenopausal patient with luminal, grade 2, T1b, N0 breast cancer, and to give such patient adjuvant chemotherapy if proved to have high risk by mamma print assay. St. Gallen panelists did not recommend that. Lastly E-panel, opposite to S-panel, favored adding platinum-based neo/adjuvant chemotherapy to patients with BRCA1 or BRCA2 mutations. In our opinion, some of these controversial clinical conditions together with the other 9 situations where there was no consensus even among S-panel are subject to further joint research both on local and international levels. One of the important issues that currently face the oncology profession is the financial inability that prevents some of patients from receiving new and costly lines of therapy in most of developing countries and even in low- and middle-income scenarios in developed countries. Many efforts have been made by authorities, international agencies dealing with cancer control, and pharmacy to try lowering drug costs ( 5 ). It is mandatory for each country to develop a national cancer registry to accurately know the number of new cancer cases every year, their specific subtypes, and to define the allocated budget to treat such patients. This would surely help in developing cost effective guidelines for the national payers. In addition to these efforts, prevention, and early diagnosis of cases are the main and successful policies to face such a problem and must be a priority for governments specially in developing counties, rather than concentrating on buying expensive drugs even those that are not yet a standard practice and are not reimbursed by insurance companies. Conclusion These guidelines are only a kind of guidance and may not apply to all patients. The best is to choose the proper adjuvant therapies to each case based on many factors such as patient preference, performance status, and physiologic age, tumor characteristics, as well as possible and affordable drugs based on both scientific and economic situations. The key to success is prevention and early diagnosis. Declarations Authors’ contributions HK: Conception of the idea and designing the study. Major contribution in writing the manuscript. HK, YW, KM: Collecting the data. HK, SF, MS, ML: Data analysis. HK, YW, KM, SF, MS, ML: Preparing the manuscript. The authors read and approved the final manuscript. Funding No fund. Availability of data and materials The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. Ethics approval and consent to participate. This study was approved by the Ethical Committee of the Egyptian National Cancer Institute. Competing interests The authors have no conflict of interest to declare. Acknowledgement Cairo University; NCI, medical oncologists : Ahmed Magdy Reba, Alfred E. Namour,Hanan E. Shafik, Hanan R. Nassar, Heba Elzawahry, Hala Aziz, Nasr Allahloubi, Thoraya Abdel Hamid, Yahia M Ismail; Surgical Oncologists : Ahmed Touny; Hatem Aboulkassem, Sharif Abdel Karim, Sherif F. Naguib and Hoda M. Abdelbaky ( Radiation Oncology ), Maha Helal ( Radiology ), Nadia Mokhtar ( Pathology ), Faculty of medicine, clinical oncologists: Amr Sakr, Emad Hamada, Hanaa Attia, Ibtessam Saadeldin Tamer El Nahas, and Omar S. Omar ( General Surgery ), Zagazig University; medical oncologists: Foad Abu Taleb, Ola M. Elfararagy, Ahmed A. Alnagar; clinical oncologists: Abd Emotaleb Mohamed, Maher Aidaros, Tanta University; clinical oncologists : Hanan Shawky, Hesham Tawfik, Lamiss M. Abdel Aziz, Nehal M. Elmashad; medical oncologist : Hosam EL-Ashtokhy, Ain Shams University; Clinical oncologists : Dina Ahmed Salem, Hesham Elghazaly, Manal M. Abdelwahab, Assiut University; clinical oncologists: HebatAllah Mahmoud Bakri, Marwa I. Abdelgawad, Samir Eid, Military medical academy ; Hany S. Attallah, Hussein Elsayed, Ossama Mohamadin Zein, Alexandria University; Abdelaziz Belal ( Clinical Oncology, faculty of medicine ), Nadia A. Abd El Moneim ( Clinical Oncology, Medical Research Institute ), Ola Sakr ( Consultant Clinical Oncology , Medical Research Institute ), Menofia University, clinical oncolgists: Eman Abdelrazek, Naser Abd El Bary, Alazhar University ; Soheir Saad shaker ( Pathology ), Wael Eisheshtawy ( clinical oncology ), Mansoura University; medical oncologists : Mohamed Aly,Tawfik Elkhodary, Helwan University ; Haytham Abdelkader ( Clinical Oncology ), Police Hospital , Gehan El-Shaarany ( Clinical Oncology Consultant ), Wadi El Neel Hospital; Marwa A. Zaied ( clinical oncologist ), MaadiArmed Forces Hospital; Mai Eissa ( Medical Oncology ), Nasser Institute for Research and Treatment ; Rasha Aboelhassan (Clinical Oncology Consultant). 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Breast Care (Basel). 2023 Apr;18(3):213-222. https://old-prod.asco.org/news-initiatives/policy-news-analysis/updated-position-statement-drug-repository-programs-aims. Becerra-Tomas N, Balducci K, Abar L, Aune D, Cariolou M, Greenwood DC, et al. Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis. Int J Cancer. 2023;152(4):616-34. Partridge AH, Niman SM, Ruggeri M, Peccatori FA, Azim HA, Jr., Colleoni M, et al. Who are the women who enrolled in the POSITIVE trial: A global study to support young hormone receptor positive breast cancer survivors desiring pregnancy. Breast. 2021;59:327-38. Pagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 2014;371:107-118. Francis PA, Regan MM, Fleming GF, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med 2015;372:436-446. https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1419. Pan H, Gray R, Davies C, et al. Predictors of recurrence during years 5-14 in 46,138 women with ER+ breast cancer allocated 5 years only of endocrine therapy (ET) {Abstract}. J Clin Oncol 34, 2016 (suppl; abstract 505) 2016. Sparano J, Gray, RJ, Wood, WC, Makower, DF, Lively, TG, Saphner, TJ et al. TAILORx: Phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score [Abstract]. J Clin Oncol 2018;36 Cardoso F, van’t Veer LJ, Bogaerts J, et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. New England Journal of Medicine 2016;375:717-729. Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol 2010;11:55-65. Luveta J, Parks RM, Heery DM, Cheung KL. Invasive Lobular Breast Cancer as a Distinct Disease: Implications for Therapeutic Strategy. Oncol Ther (2019) 1–11. doi: 10.1007/s40487-019-00105-0. Lips EH, Mukhtar RA, Yau C, de Ronde JJ, Livasy C, Carey LA, et al. Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer. Breast Cancer Res Treat (2012) 136(1):34–43. doi: 10.1007/s10549-012-2233-z. Sledge GW, Chagpar A, Perou C. Collective Wisdom: Lobular Carcinoma of the Breast. Am Soc Clin Oncol (2016) 35:18–21. doi: 10.1200/EDBK_100002. Thomas M, Li H, Abraham J, Moore HCF, Budd GT, Montero AJ, et al. Comparison of survival outcomes between treatment with endocrine therapy and chemoendocrine therapy in patients with invasive lobular carcinoma. Cancer Res (2019) 80(4 Suppl):Abstract nr P2-14-13. doi: 10.1158/1538-7445.SABCS19-P2-14-13. Conlon N, Ross DS, Howard J, Catalano JP, Dickler MN, Tan LK. Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma? Breast J (2015) 21(5):514–9. doi: 10.1111/tbj.12445. Santa-Maria C, O’Donnell M, Nunes R, et al. Integrating Immunotherapy in Early-Stage Triple-Negative Breast Cancer: Practical Evidence-Based Considerations. J Natl Compr Canc Netw 2022 July; 20(7): 738–744. doi:10.6004/jnccn.2022.7025. Schmid P, Cortes J, Dent R, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med 2022;386:556–567. Schmid P, Park YH, Ferreira M, et al. KEYNOTE-522: phase 3 study of neoadjuvant pembrolizumab + chemotherapy versus placebo 1 chemo-therapy, followed by adjuvant pembrolizumab versus placebo for early triple-negative breast cancer: pathologic complete response in key subgroups and by treatment exposure and residual cancer burden. Ann Oncol 2019;30(Suppl 5):Abstract 1812. Cortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014;384:164-172. Yu EY, Massard C, Retz M, et al. KEYNOTE-365 cohort a: pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) [abstract]. J Clin Oncol 2019;37(Suppl):Abstract 145. Tolaney SM, Barry WT, Dang CT, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med 2015;372:134-141. Kim J, Kook Y, Jang J, et al. Adjuvant trastuzumab plus pertuzumab (TP) versus trastuzumab (T) alone in patients achieving pathologic complete response after chemotherapy with TP. Annals of oncology 2022; ABSTRACT 33(7) S614. Tutt A, Garber J, Kaufman B, et al. OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021;384(25):2394-2405. Additional Declarations No competing interests reported. Supplementary Files Supplement1.pdf Supplement2.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4251493","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":292322170,"identity":"acae79fb-a5eb-4e43-a4c0-09237e736b18","order_by":0,"name":"Hussein Khaled","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYBACgxtgSoLBvr354AMgi4ePkBbDGVAtBjzHkg1AWtgIaTGWgFknkWMGZhPUYibdY/zxR4VFnjlDWlrl1xw7GTYG5oePbuDRYiNzxkya54xEsWXD4WO3ZbclAx3GZmycg08L0D3MjG0SiQ0H29JuS25jBmrhYZPGp8VMIsf4489/QC2HecyKJbfVE9ZiLJFjIMHbIJG44RiPGePHbYcJazGckVYmzXNMInFmD1uyNOO24zxszAT8YnAjefPHHzV1if3yjw9+/Lmt2p6fvfnhY3xaUAAzD5gkVjkIMP4gRfUoGAWjYBSMGAAA+vVFmLyHikgAAAAASUVORK5CYII=","orcid":"","institution":"National Cancer Institute, Cairo University","correspondingAuthor":true,"prefix":"","firstName":"Hussein","middleName":"","lastName":"Khaled","suffix":""},{"id":292322172,"identity":"712af936-d1d6-4d78-8eb4-710fe1f7f217","order_by":1,"name":"Yousry Wasef Nada","email":"","orcid":"","institution":"Maadi Armed Forces Medical Compound","correspondingAuthor":false,"prefix":"","firstName":"Yousry","middleName":"Wasef","lastName":"Nada","suffix":""},{"id":292322173,"identity":"1fccb184-abcc-4b66-8a0b-138613623e30","order_by":2,"name":"Kareem Mohamed Ramadan","email":"","orcid":"","institution":"Maadi Armed Forces Medical Compound","correspondingAuthor":false,"prefix":"","firstName":"Kareem","middleName":"Mohamed","lastName":"Ramadan","suffix":""},{"id":292322174,"identity":"c4ad7a08-d1ad-44e6-b494-2f255a8c6090","order_by":3,"name":"Shawkat Fekry","email":"","orcid":"","institution":"Maadi Armed Forces Medical Compound","correspondingAuthor":false,"prefix":"","firstName":"Shawkat","middleName":"","lastName":"Fekry","suffix":""},{"id":292322175,"identity":"ceb41fdc-b728-42f2-8cac-781d9fa53e3f","order_by":4,"name":"Mohamed Samy Seleam","email":"","orcid":"","institution":"Maadi Armed Forces Medical Compound","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"Samy","lastName":"Seleam","suffix":""},{"id":292322176,"identity":"3df2b907-df53-45fa-9c70-8e2e10d12ca1","order_by":5,"name":"Mohamed Lotayef","email":"","orcid":"","institution":"National Cancer Institute, Cairo University","correspondingAuthor":false,"prefix":"","firstName":"Mohamed","middleName":"","lastName":"Lotayef","suffix":""}],"badges":[],"createdAt":"2024-04-11 09:22:01","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4251493/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4251493/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":55322606,"identity":"77f7d742-817d-4131-8917-24f86a632c6a","added_by":"auto","created_at":"2024-04-25 16:28:44","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":89816,"visible":true,"origin":"","legend":"\u003cp\u003eSee image above for figure legend\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-4251493/v1/343a2835de72933de16498aa.png"},{"id":55323408,"identity":"b42acda2-d405-416e-9ff2-6603bb2883ab","added_by":"auto","created_at":"2024-04-25 16:44:47","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":935539,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4251493/v1/99e49baf-d083-4c74-bd17-089590311626.pdf"},{"id":55322603,"identity":"18ad2900-5941-4342-ad28-6985458d8249","added_by":"auto","created_at":"2024-04-25 16:28:42","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":596312,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement1.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4251493/v1/0989b75a0810fccc260eb4aa.pdf"},{"id":55323176,"identity":"f7a346d6-c10a-4015-a24e-86acd5f1960b","added_by":"auto","created_at":"2024-04-25 16:36:42","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":30299,"visible":true,"origin":"","legend":"","description":"","filename":"Supplement2.docx","url":"https://assets-eu.researchsquare.com/files/rs-4251493/v1/eaf2484fa94072307f76dd31.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"St. Gallen early breast cancer management recommendations are becoming more applicable to most countries even with different levels of income and healthcare scenarios, Egypt as an example","fulltext":[{"header":"Introduction","content":"\u003cp\u003eThe 18th St. Gallen Consensus Conference on early breast cancer treatment was held in Vienna in March 2023. On the last day of the meeting, the 70 members of the panel discussed and voted on recent clinical research findings focusing on diagnosis, and therapy guidelines aiming to optimize early breast cancer patient diagnosis and treatment (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eSubsequently, and as was done previously (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e), a monkey survey vote was arranged to vote on some of the controversial issues of early breast cancer management that are more relevant to Egyptian patients.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eA steering committee prepared survey questions that were adapted from the 18th St. Gallen (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e), with some adaptation to suit the Egyptian situation. Then, the prepared questions were delivered online through the monkey survey website: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.Surveymonkey.Com\u003c/span\u003e\u003cspan address=\"https://www.Surveymonkey.Com\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. The survey was formed of 100 questions, and the answers were reported in percentages. A blank box was included with every question so the voter may express any additional comment(s) or explain in more detail her/his answer. After 3 weeks of online projection, the answers and data were collected and analyzed by the steering committee in preparation for writing the manuscript, which was then distributed and shared by the whole group for any further comments.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003eThe detailed questions and answers of the voting results of the E-panel as well as graphic projections of a detailed comparison between the original St Gallen answers (\u003cspan\u003e4\u003c/span\u003e) vs. the Egyptian voting results for the same shared questions are shown in the supplement 1. Supplement 2 illustrates and summarizes Egyptian panel (E-panel) voting for questions where the results were either recommend (\u0026ge;\u0026thinsp;50%) or strongly recommend (\u0026ge;\u0026thinsp;75%). It also compares voting results between E-panel and St Gallen panel (S-panel). The following text will illustrate only items that gained endorsement of the E-panel by \u0026gt;\u0026thinsp;50% of voters.\u003c/p\u003e\n\u003cdiv id=\"Sec4\"\u003e\n \u003ch2\u003eGeneral Practice Issues\u003c/h2\u003e\n \u003cp\u003eWhile 95% of E-panel expressed situations where drug costs prevent some patients from receiving important therapies, only 43% of S-panel positively reported on this issue. Most developing countries, in some European countries, and even in certain areas in the US authorities are facing this situation. ASCO has been discussing this problem focusing on equity of care. They have done a lot in terms of supporting the states for drug repository programs. Also, some US societies have put forward programs to find a way to repurpose those drugs (\u003cspan\u003e5\u003c/span\u003e). In addition, one way to solve this problem is to bring people together, so having members of the government, from industry, physicians to discuss prices and strict guideline applications is also important, so that physicians would not be caught in the middle and don\u0026rsquo;t have the resources to maintain their practices.\u003c/p\u003e\n \u003cp\u003eBurnout was also discussed. Thirty-seven percent an additional panel reported burnout themselves, and additional 38% consider burnout of a significant concern for many colleagues. These percentages were reported to be 12%, and 79%, respectively for the S-panel. In the opinion of E-voters, the causes of burnout were either because of inadequate healthcare systems (45%), or due to excessive clinical load (32%). The same was expressed by the S-voters, being 60% and 12%, respectively. Then attention was directed to breast cancer survivors\u0026rsquo; well-being. On asking \u0026ldquo;in patients with body mass index (BMI) of more than 25, is there a specific diet that can lower the risk of breast cancer recurrence?\u0026rdquo;. The S-panel was not convinced by (No 73%), while there was no consensus between members of the E-panel (48% Yes, and 34% No), but by a clear majority (83% and 81%, respectively) both panels voted that keeping lower BMI is of general value as suggested by a meta-analysis recently published (\u003cspan\u003e6\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe S-panel (70%) voted to recommend acupuncture to alleviate arthralgia caused by aromatase inhibitor treatment or neuropathy induced by chemotherapy. On the contrary, the E-panel voted against its routine use (63%).\u003c/p\u003e\n \u003cp\u003eA case of a young patient treated by tamoxifen / ovarian function suppression as an adjuvant therapy for patients with 4 or more involved axillary lymph nodes and she wants to get pregnant was presented. The panels were asked if it is possible to interrupt endocrine therapy after 2 years in view of IBCSG / BIG / Alliance POSITIVE trial data (\u003cspan\u003e7\u003c/span\u003e). Seventy-nine percent of the S-panel and 56% of the E-panel would not encourage her getting pregnant. This voting recommendation would be since the POSITIVE trial included only very few patients with \u0026ge;\u0026thinsp;4 involved axillary nodes. In response to a question whether postmenopausal women on AI treatment for ER positive breast cancer should not be offered intravaginal estrogens because of concerns over systemic estrogen exposure and impact of adjuvant treatment efficacy, 58% of S-panel did not agree, while 56% of E-panel agree on this advice.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec5\"\u003e\n \u003ch2\u003ePathology\u003c/h2\u003e\n \u003cp\u003eBoth panels were not convinced that stromal tumor-infiltrating lymphocytes (TILs) routine testing is to be used to assess breast cancer risk of recurrence. They voted by a clear majority to give adjuvant chemotherapy to 2 early breast cancer case examples; the first case was 43 old women that has undergone lumpectomy for 1.6 cm, node-negative, grade3, triple negative breast cancer (TNBC). TILs were 75%. The second case has undergone surgery for stageT1b TNBC, for a tumor measuring 0.8 cm, and had a high TILs\u0026thinsp;\u0026gt;\u0026thinsp;50%.\u003c/p\u003e\n \u003cp\u003eOn another issue, both panels voted (\u0026gt;\u0026thinsp;90%) that breast cancer patients should have access to genetic counselors. Also, and as shown in Table \u003cspan\u003e1\u003c/span\u003e, the panels were discussing risk-reducing measures with a woman who has been diagnosed with early stage breast cancer. They were asked if they would preferentially recommend either risk-reducing surgery, or intensive (mammogram and MRI-based) screening for both pre- and post-menopausal women with BRCA1, BRCA2, PALB2, ATM, and CHEK2 mutations. Most of the E-panel (\u0026gt;\u0026thinsp;50%) preferred intensive screening for all subtypes except pre-menopausal women with either BRCA1 or BRCA2 mutations where they preferred doing risk-reducing surgery. On the other hand, the S-panel preferred surgery both pre- and post-menopausal women with BRCA1, and BRCA2 mutations. They also preferred surgery by a narrow vote (42% vs 32%) for pre-menopausal women with PALB2 mutations.\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eTable 1. Types of risk-reducing measures with a woman with early stage breast cancer\u003c/strong\u003e\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"left\" width=\"786\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.353689567430024%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eTopic\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e(Question no.)\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003e\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"27.608142493638677%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eChoice\u003c/strong\u003e\u003c/p\u003e\n \u003cp\u003e\u003cstrong\u003eE-panel recommendation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"26.59033078880407%\" colspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eS-panel recommendation\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.447837150127228%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eConsensus between E-panel and S-panel\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"100%\" colspan=\"6\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e(Qs:16-25) : You are discussing risk-reducing mastectomy and intensified surveillance with a woman who has been diagnosed with early stage breast cancer. She has had genetic testing and harbors a deleterious mutation. As part of a shared decision making process, she asks your opinion on management. Indicate if you would preferentially recommend either contralateral risk-reducing surgery, or intensive (mammogram and MRI-based) screening, or no preference (either) if she is\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.353689567430024%\" rowspan=\"2\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eGenetic mutation and menopausal status\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"72.64631043256998%\" colspan=\"5\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eChoice\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"18.07017543859649%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"20%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntensive screening\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.24561403508772%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eSurgery\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.24561403508772%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003eIntensive screening\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"25.43859649122807%\" valign=\"top\"\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.388535031847134%\" valign=\"top\"\u003e\n \u003cp\u003epremenopausal with BRCA1 mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.121019108280255%\" valign=\"top\"\u003e\n \u003cp\u003e55%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.522292993630574%\" valign=\"top\"\u003e\n \u003cp\u003e40%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e67%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e13%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.471337579617835%\" valign=\"top\"\u003e\n \u003cp\u003econsensus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.388535031847134%\" valign=\"top\"\u003e\n \u003cp\u003epostmenopausal with\u0026nbsp;BRCA1 mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.121019108280255%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e41%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.522292993630574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e53%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e61%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e17%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.471337579617835%\" valign=\"top\"\u003e\n \u003cp\u003eNo consensus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.388535031847134%\" valign=\"top\"\u003e\n \u003cp\u003epremenopausal with\u0026nbsp;BRCA2 mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.121019108280255%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e50%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.522292993630574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e47%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e63%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e14%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.471337579617835%\" valign=\"top\"\u003e\n \u003cp\u003econsensus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.388535031847134%\" valign=\"top\"\u003e\n \u003cp\u003e\u0026nbsp;postmenopausal with BRCA2 mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.121019108280255%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e33%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.522292993630574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e57%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e42%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e32%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.471337579617835%\" valign=\"top\"\u003e\n \u003cp\u003eNo consensus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.388535031847134%\" valign=\"top\"\u003e\n \u003cp\u003epremenopausal with\u0026nbsp;PALB2 mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.121019108280255%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e30%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.522292993630574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e53%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e42%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e32%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.471337579617835%\" valign=\"top\"\u003e\n \u003cp\u003eNo consensus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.388535031847134%\" valign=\"top\"\u003e\n \u003cp\u003epostmenopausal with\u0026nbsp;PALB2 mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.121019108280255%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e23%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.522292993630574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e57%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e20%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e53%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.471337579617835%\" valign=\"top\"\u003e\n \u003cp\u003econsensus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.388535031847134%\" valign=\"top\"\u003e\n \u003cp\u003epremenopausal with\u0026nbsp;ATM mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.121019108280255%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e20%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.522292993630574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e57%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e9%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e73%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.471337579617835%\" valign=\"top\"\u003e\n \u003cp\u003econsensus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.388535031847134%\" valign=\"top\"\u003e\n \u003cp\u003epostmenopausal with\u0026nbsp;ATM mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.121019108280255%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e22%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.522292993630574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e57%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e79%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.471337579617835%\" valign=\"top\"\u003e\n \u003cp\u003econsensus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.388535031847134%\" valign=\"top\"\u003e\n \u003cp\u003epremenopausal with\u0026nbsp;CHEK2 mutation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.121019108280255%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e22%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.522292993630574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e58%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e8%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e71%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.471337579617835%\" valign=\"top\"\u003e\n \u003cp\u003econsensus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd width=\"27.388535031847134%\" valign=\"top\"\u003e\n \u003cp\u003ePostmenopausal with\u0026nbsp;CHEK2 mutation\u0026nbsp; \u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.121019108280255%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e20%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"14.522292993630574%\" valign=\"top\"\u003e\n \u003cp\u003e\u003cstrong\u003e60%\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e1%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"13.248407643312103%\" valign=\"top\"\u003e\n \u003cp\u003e79%\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd width=\"18.471337579617835%\" valign=\"top\"\u003e\n \u003cp\u003econsensus\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003cdiv\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec6\"\u003e\n \u003ch2\u003eDCIS\u003c/h2\u003e\n \u003cp\u003eBoth the E-panel and the S-panel recommended radiation therapy for a woman being either pre- or post-menopausal that has undergone breast conserving surgery for DCIS and this DCIS is grade 1 to 2, without comedo necrosis, and \u0026lt;\u0026thinsp;2 cm in diameter, even if the tumor is ER\u0026thinsp;+\u0026thinsp;ve (Table \u003cspan\u003e2\u003c/span\u003e). On the other hand, both panels would not recommend receiving radiation therapy after breast conserving surgery for women aged\u0026thinsp;\u0026gt;\u0026thinsp;70 years and having tumors\u0026thinsp;\u0026lt;\u0026thinsp;2 cm with or without comedo necrosis. For women aged 65 years or less, both panels agreed to give radiation therapy if the tumor is \u0026lt;\u0026thinsp;2 cm with or without comedo necrosis, and recommendations were stronger if patients\u0026rsquo; age was \u0026lt;\u0026thinsp;50 years.\u003c/p\u003e\n \u003cdiv\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv\u003eTable 2\u003c/div\u003e\n \u003cdiv\u003e\n \u003cp\u003eIndications of radiotherapy in cases of DCIS\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eTopic\u003c/p\u003e\n \u003cp\u003e(Question no.)\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" colspan=\"2\"\u003e\n \u003cp\u003eEgyptian Consensus\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eS-panel recommendation\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\" rowspan=\"2\"\u003e\n \u003cp\u003eConsensus between E-panel and S-panel\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRecommend*\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStrongly recommend*\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eA healthy woman has undergone breast conserving surgery for DCIS. This DCIS is grade 1 to 2, without comedo necrosis, and less than 2 cm in diameter. Being premenopausal, should she receive radiation therapy? (Q26)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIf the above woman is postmenopausal? (Q27)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (72%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIf the above woman is premenopausal and being ER\u0026thinsp;+\u0026thinsp;will take endocrine therapy? (Q28)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (62%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age above 70, DCIS smaller than 2 cm: would you give radiation therapy? (Q31).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo (52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age above 70, DCIS smaller than 1 cm: would you give radiation therapy? (Q32).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo (64%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age above 70, DCIS without comedonecrosis: would you give radiation therapy? (Q33).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo (63%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo (55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age above 70, DCIS smaller than 2 cm without comedonecrosis: would you give radiation therapy? (Q34).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo (59%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo (73%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age 50\u0026ndash;65, DCIS smaller than 2 cm: would you give radiation therapy? (Q35).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age 50\u0026ndash;65, DCIS smaller than 1 cm: would you give radiation therapy? (Q36).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (50%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age 50\u0026ndash;65, DCIS without comedonecrosis : would you give radiation therapy? (Q37).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (52%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age 50\u0026ndash;65, DCIS smaller than 2 cm without comedonecrosis : would you give radiation therapy? (Q38).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (54%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (42%)\u003c/p\u003e\n \u003cp\u003eNo (38%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo consensus among members of S-panel\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age below 50, DCIS smaller than 1 cm : would you give radiation therapy? (Q39).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (73%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age below 50, DCIS smaller than 2 cm : would you give radiation therapy? (Q40).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (55%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (61%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age below 50, DCIS without comedonecrosis: would you give radiation therapy? (Q41).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (75%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePatients who have undergone breast conserving surgery for DCIS, with margins greater than 2 mm., age below 50, DCIS, smaller than 2cm without comedonecrosis: would you give radiation therapy? (Q42).\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (66%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\u0026nbsp;\u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYes (60%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003econsensus between both panels\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n \u003c/div\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec7\"\u003e\n \u003ch2\u003eSurgery\u003c/h2\u003e\n \u003cp\u003eIn case of a patient who has undergone neoadjuvant treatment with AC/T chemotherapy regimen, with a significant clinical response, and at surgery, there is residual disease in the axilla. The tumor is triple negative with nodal burden macrometastasis in 1 of 3 SLN. Panelists were asked if they would recommend completion of axillary dissection or axillary radiation. E-panel recommended axillary lymph node dissection by 55%, while S-panel voted for the same choice by 47%.\u003c/p\u003e\n \u003cp\u003eAnother case was exhibited as \u0026ldquo;A 63 year old woman was treated 9 years ago for a stage 2 node-negative breast cancer with lumpectomy and radiation therapy, as well as adjuvant systemic endocrine therapy that stopped 2 years ago. Now she has had ipsilateral tumor recurrence. No more than grade 1 or only very localized grade 2 side effects at the level of the skin and/or the soft tissues are present. The tumor is ER+/Her2-. Staging scans are negative. The lesion is less than 2 cm in size, 3 cm from nipple, and would be amenable to breast conserving surgery with acceptable aesthetic results\u0026rdquo; Both panels recommended doing mastectomy (59% and 74% votes of E- and S-panels, respectively).\u003c/p\u003e\n \u003cp\u003eAnother patient was discussed. While she was receiving adjuvant aromatase inhibitor, developed isolated local recurrence. Her disease was strongly\u0026thinsp;+\u0026thinsp;ve ER and -ve HER2. Her local recurrence was fully excised. The patient did not receive adjuvant chemotherapy. When asked about further management, both panels recommended adjuvant chemotherapy (54%, and 63% of E- and S-panels respectively).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec8\"\u003e\n \u003ch2\u003eRadiation therapy\u003c/h2\u003e\n \u003cp\u003eBoth panels endorsed (\u0026gt;\u0026thinsp;65%) moderate hypofractionation as the preferred radiation schedule for chest wall irradiation irrespective of nodal irradiation after mastectomy, after breast conserving surgery for invasive cancer, and by \u0026gt;\u0026thinsp;55% after breast conserving surgy for DCIS. Also, both panels agreed that for routine radiation therapy for early breast cancer, there is at present no clinical advantage to proton therapy over photon therapy (\u0026gt;\u0026thinsp;65%).\u003c/p\u003e\n \u003cp\u003eA boost dose of radiation therapy to the primary tumor bed after breast conserving surgery was approved and indicated by 50% of the E-panel in patients with at least 1 of the 4 following prognostic factors: high grade cancers, extensive intraductal component, TNBC or HER2- positive subtypes, and age below 50 years. However, no consensus was reached among members of S-panel regarding the number of prognostic factors needed to give a boost dose.\u003c/p\u003e\n \u003cp\u003eWhile 63% of the S-panel agree on the most important clinical observation from the PRIME-II that radiation lowers in-breast recurrence and therefore is effective, only 54% of the E-panel endorsed this statement. Then both panels were asked a series of questions on the role of post mastectomy radiation therapy in relation to both tumor size (T2, and T3), and to its biologic subtype (ER\u0026thinsp;+\u0026thinsp;ve, HER2\u0026thinsp;+\u0026thinsp;ve, and TNBC). As shown in Fig.\u0026nbsp;1. It is obvious that with increasing disease burden the percentage of recommending post mastectomy goes up specially for HER2\u0026thinsp;+\u0026thinsp;and TN tumors. The Egyptian survey did not include some questions on higher tumor burden when it was clear that voters recommend post mastectomy radiotherapy in lower earlier tumor stages. The S-panel did not recommend radiation in case of deleterious ATM gene mutation, while the E-panel split in their answers (29% yes, 32% no, and 39% abstain).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec9\"\u003e\n \u003ch2\u003eAdjuvant endocrine therapy in premenopausal patients\u003c/h2\u003e\n \u003cp\u003eFifty percent of E-panel recommended tamoxifen and OFS while 31% of S-panel advised AI and OFS for IDC G2 (T1 N0) with low recurrence score. Published data of SOFT and TEXT trials, showed a DFS of 92.8% in the exemestane plus ovarian suppression group, compared to 88.8% in the tamoxifen/ovarian suppression group (HR for recurrence, 0.66; 95% CI, 0.55\u0026ndash;0.80; P\u0026thinsp;\u0026lt;\u0026thinsp;.001). On the other hand, OS data was not significantly different between both groups (HR for death in the exemestane plus ovarian suppression group, 1.14; 95% CI, 0.86\u0026ndash;1.51; P\u0026thinsp;=\u0026thinsp;.37). The NCCN guidelines included an aromatase inhibitor/ovarian suppression for 5 years as an adjuvant endocrine therapy option for premenopausal patients with HR positive cases at higher risk of recurrence e.g., young age, high-grade tumor, and lymph-node involvement (\u003cspan\u003e8\u003c/span\u003e, \u003cspan\u003e9\u003c/span\u003e)\u003c/p\u003e\n \u003cp\u003eFor assessing functional menopause in a patient who is 38 years of age and is amenorrheic and experiencing menopausal symptoms while receiving GnRH agonist and AI therapy, 44% of S-panel voted for semiannual monitoring of estradiol levels vs. 37.5% in E-panel. However, 37% of S-panel considered no additional test vs. 21% of E-panel.\u003c/p\u003e\n \u003cp\u003eOvarian function suppression induces amenorrhea and reduces ovarian estrogen synthesis without causing permanent menopause, so menopausal status in those receiving ovarian function suppression cannot be determined. Thus standard criteria for the diagnosis of menopause in patients with breast cancer are lacking (\u003cspan\u003e10\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eIt was also recommended by a clear majority of both St. Gallen (65%) and Egyptian (63%) panels to give monthly GnRH agonist in any premenopausal patient that has had breakthrough menstrual bleeding while receiving GnRH every 12 weeks.\u003c/p\u003e\n \u003cp\u003eRegarding extended endocrine therapy for patient with stage 3 breast cancer that has received 5 years of AI plus ovarian suppression, and she has had substantial arthralgia but otherwise found treatment to be acceptable, the higher percentage of voting in St. Gallen (35%) was for\u003c/p\u003e\n \u003cp\u003econtinuation with tamoxifen while 23% of the Egyptian side voted for discontinuation of therapy.\u003c/p\u003e\n \u003cp\u003eAdjuvant endocrine therapy is recommended for a minimum of 5 years. A retrospective analysis by Oxford University studied risk of recurrence for years 5 through 20 after 5 years of endocrine therapy. These data showed a considerable risk of recurrence between years 5 and 20 in these patients treated with initial 5 years of endocrine therapy. Data has now emerged showing benefit of extended endocrine therapy in improving DFS (\u003cspan\u003e11\u003c/span\u003e). The NCCN Guidelines for Breast Cancer recommend 5 years of tamoxifen with or without ovarian suppression (category 1) or ovarian suppression plus an aromatase inhibitor for 5 years (category 1).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec10\"\u003e\n \u003ch2\u003eAdjuvant therapy in postmenopausal patients\u003c/h2\u003e\n \u003cp\u003eThere was a great difference between the two panels when asked about doing a genomic signature assay for a patient with luminal breast cancer grade 2 T1b N0, as 74% of S-panel voted for not doing the assay, while 53% of the E-panel voted for doing it.\u003c/p\u003e\n \u003cp\u003eFor patients with invasive ductal or lobular tumors greater than 0.5 cm in diameter and lymph node-negative patients, the NCCN recommendation is strongly considering the 21-gene RT-PCR\u003c/p\u003e\n \u003cp\u003eassay to help estimate likelihood of recurrence and benefit from chemotherapy.\u003c/p\u003e\n \u003cp\u003eAn exploratory analysis from the TAILORx study, showed that adjuvant chemotherapy may be considered in patients 50 years of age or younger with a 21-gene RS of 16\u0026ndash;25. Also, patients with T1b tumors with low grade histology should be considered for endocrine monotherapy, as the TAILORx study did not include patients with such tumors (\u003cspan\u003e12\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec11\"\u003e\n \u003ch2\u003eNeo/adjuvant chemotherapy\u003c/h2\u003e\n \u003cp\u003eThere was also a discordance between the two panels as regard prescribing adjuvant chemotherapy for a 57 year old patient who has grade 2 luminal breast cancer (T1b N0) with high genomic risk by MammaPrint assay as 69% of S-panel did not recommend adjuvant chemotherapy while 75% of the E-panel recommended chemotherapy. For the same case but assuming that tumor size was T2N0 instead of T1No, both panels agreed by a clear majority (78% and 86%, respectively) to give adjuvant chemotherapy.\u003c/p\u003e\n \u003cp\u003eConsidering recommending adjuvant chemotherapy for the same case criteria but detailing the decision based on tumor size, a sum of 56% of S-panel agreed to give adjuvant chemotherapy if tumor size was 1 cm or more, and 22% voted for not giving chemotherapy for stage I tumor like this. On the other hand, 55% of the E-panel voted for giving chemotherapy regardless of tumor size.\u003c/p\u003e\n \u003cp\u003eResults from the randomized MINDACT trial, demonstrated that among patients at low clinical risk/ high genomic risk, 5-year survival with no distant metastasis was 95.8% with chemotherapy (95% CI, 92.9 to 97.6), compared with a rate of 95.0% (95% CI, 91.8 to 97.0%) without chemotherapy (adjusted HR for distant metastasis or death with chemotherapy vs. no chemotherapy,1.17; 95% CI, 0.59 to 2.28). These data suggest that the results of the 70-gene signature do not provide evidence for making recommendations regarding chemotherapy for patients at low clinical risk (\u003cspan\u003e13\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eIn case of a postmenopausal patient that has had IDC, G1, luminal A, ki 67\u0026thinsp;\u0026lt;\u0026thinsp;15%, and low recurrence score, 6%,14%, and 62% of S-panel while 21%,14%, and 39% of E-panel voted for 2, 3, and 4 positive lymph nodes, respectively as the number of positive axillary lymph nodes that would prompt recommending adjuvant chemotherapy. It is worth mentioning that for patients with four or more involved nodes, the NCCN guidelines recommends systemic adjuvant chemotherapy followed by endocrine therapy. While a secondary analysis of the prospective SWOG 1118 trial demonstrated no benefit for chemotherapy for patients with 1\u0026ndash;3 involved ipsilateral axillary lymph nodes and a low RS, there was benefit for the addition of adjuvant chemotherapy in those with high-RS (\u0026ge;\u0026thinsp;31) from the 21-gene assay (\u003cspan\u003e14\u003c/span\u003e). In the MINDACT trial, among patients with 1\u0026ndash;3 positive nodes who had a high clinical risk of recurrence but low risk by the 70-gene assay, the rates of survival were similar between those who received adjuvant chemotherapy in addition to adjuvant endocrine therapy versus those received adjuvant endocrine therapy alone, suggesting that chemotherapy could be omitted in this group (\u003cspan\u003e13\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eIn case of invasive lobular carcinoma without pleomorphism, luminal A, stage 1\u0026ndash;3, grade 1\u0026ndash;2, 60% of S-panel recommended giving neo/adjuvant chemotherapy, but the Egyptian team was divided between supporters and opponents of neo/adjuvant chemotherapy for such a case.\u003c/p\u003e\n \u003cp\u003eData showed that ILC had poor response to chemotherapy leading to lower OS rates following NAC compared to those observed in IDC (\u003cspan\u003e15\u003c/span\u003e). In part, this was explained by the less frequent pCR occurring in ILC subset. An analysis of a large set of data comprising two NAC trials that have included 676 patients showed that 75% of cases had ILC (\u003cspan\u003e16\u003c/span\u003e). Following neoadjuvant chemotherapy, pCR rates were significantly less likely to be achieved in ILC than hallmark in IDCs cases (11% versus 25%). ILC poor chemo-sensitivity could be explained by its different biological characteristics. These characteristics include low grade, low mutational burden, ER positivity, and a low rate of proliferation assessed with Ki-67 (\u003cspan\u003e17\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eAfter addition of low genomic signature score to the previous case, 63% of ST Gallen changed voting and agreed not to give neo/adjuvant chemotherapy, while the E-panel was still confused between the two opinions. Comparing the use of endocrine plus chemotherapy vs. endocrine therapy alone in patients with ILC (\u003cspan\u003e18\u003c/span\u003e), no survival difference was observed between both arms. Also, Oncotype Dx testing in ILC patients revealed that most cases would receive little benefit from chemotherapy. With more data, gene signatures assays may prove to be a vital tool in choosing chemotherapy for ILC patients (\u003cspan\u003e19\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec12\"\u003e\n \u003ch2\u003eTriple Negative Therapy\u003c/h2\u003e\n \u003cp\u003eBoth Egyptian and S-panel agreed by a similar percentage (78%) that carboplatin-containing regimen should be included given to patients receiving neoadjuvant therapy for stage 2 or 3 TBC who are also receiving taxane, anthracycline, and cyclophosphamide based chemotherapy, even when pembrolizumab is being administered.\u003c/p\u003e\n \u003cp\u003eDose density is associated with improved EFS and OS benefits in anthracycline- and taxane-based regimens. The KEYNOTE-522 regimen (which included pembrolizumab) did not include dose-dense AC, and thus the benefits observed with this regimen, are independent of dose density. There are practical considerations of substituting an every-2-week AC with an every-3-week regimen. But this would increase the complexity of the regimen, in terms of not only additional visits but also uncertainty regarding duration of pembrolizumab, because AC would finish several weeks earlier. Although studies evaluating dose density suggest acceptable toxicity profiles compared with non\u0026ndash;dose-dense chemotherapy, the toxicity and feasibility of dose density after 3 months of carboplatin and paclitaxel with pembrolizumab is unknown (\u003cspan\u003e20\u003c/span\u003e). For these reasons, 46% of E-panel and 38% of S-panel were unsure about replacing 3-week approach with dose dense one.\u003c/p\u003e\n \u003cp\u003eAdvising adjuvant pembrolizumab after achieving pCR in the above example was also discussed. Although the two panels agreed to continue adjuvant pembrolizumab after pCR (59% and 66% of the E- and S-panels, respectively), there was a considerable percentage (32%) that couldn\u0026rsquo;t be neglected in S-panel who preferred to not to give the drug. The lower percentage of the E-panel may be explained by the affordability of the drug due to its high cost.\u003c/p\u003e\n \u003cp\u003eIn the KEYNOTE trial, EFS benefit in those achieving pCR was almost identical between the control and experimental arms (92.5% vs 94.4%, respectively). This analysis was exploratory and was not powered to make a definitive conclusion. However, this should be considered in the context of the wealth of data demonstrating the association of pCR with high EFS rates for individuals achieving pCR. Furthermore, although most of the toxicity of the KEYNOTE-522 regimen was seen in the neoadjuvant portion of treatment, the toxicity of single-agent pembrolizumab given in the adjuvant sitting was not negligible (\u003cspan\u003e21\u003c/span\u003e). Given the unclear benefit of adjuvant pembrolizumab in those achieving pCR, and the demonstrated toxicity in the adjuvant phase of treatment, clinicians may discuss potential benefits versus toxicity with individuals to determine whether to continue adjuvant pembrolizumab.\u003c/p\u003e\n \u003cp\u003eThe preferred approach for a 60 year old female patient with TNBC having T2N0 disease was neoadjuvant chemotherapy and pembrolizumab in 65% of S-panel and 46% in E-panel. Thirty percent 30% of E-panel voted for neoadjuvant chemotherapy only vs. 22% in S-panel. The KEYNOTE-522 results need to be considered in the context of its toxicity; a 77.1% high-grade treatment-related adverse events rate is very high, and ideally alternative less toxic treatment regimens should be considered, especially in patients in whom the benefit of pembrolizumab is less clear. Subgroup analysis, albeit exploratory and with relatively small numbers, demonstrated less apparent benefit in those with a performance status of 1 and in older patients (\u003cspan\u003e22\u003c/span\u003e). So standard dose-dense AC/paclitaxel may be considered in older patients and/or those with a performance status\u0026thinsp;\u0026gt;\u0026thinsp;0, especially those with node-negative disease.\u003c/p\u003e\n \u003cp\u003eApproximately the same percent in both panels (~\u0026thinsp;42%) agreed to do primary surgery for stage 1 TNBC that clinically have no indication for neoadjuvant treatment, while 46% in S-panel and 25% in E-panel recommended \u0026lsquo;chemotherapy only\u0026rsquo; as an appropriate neoadjuvant therapy for small TNBC tumors. pCR to preoperative systemic therapy is associated with an extremely favorable DFS and OS rates, particularly in situations in which all treatment is given preoperatively. These correlations are strongest for TNBC, somewhat less so for HER2-positive disease, and least for ER-positive disease (\u003cspan\u003e23\u003c/span\u003e). According to NCCN guidelines, preoperative systemic therapy is preferred for TNBC, if\u0026thinsp;\u0026ge;\u0026thinsp;cT2 or \u0026ge;\u0026thinsp;cN1 and preoperative systemic therapy can be considered for cT1c, cN0 TNBC. The KEYNOTE-522 study enrolled patients with stage II or III TNBC, and therefore, any patient meeting these criteria should be considered for chemotherapy and pembrolizumab (\u003cspan\u003e21\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe panels were asked if it is indicated to give adjuvant pembrolizumab in addition to standard chemotherapy for triple negative breast cancer patient who was treated with primary surgery and had positive lymph node. Most of S-panel (62%) were against this approach while 46% in E-panel agreed to give adjuvant pembrolizumab as well. Based on NCCN guidelines, adjuvant pembrolizumab is recommended only if pembrolizumab-containing regimen was given preoperatively (\u003cspan\u003e10\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eAnother adjuvant consideration in patients with residual disease concerns those with germline BRCA mutations. Addition of olaprib to pembrolizumab in adjuvant setting was suggested by 62% of ST Gallen panel but the Egyptian panel, 32% preferred to give the drugs in sequence.\u003c/p\u003e\n \u003cp\u003eAlthough adjuvant XXXlaparib was not part of the KEYNOTE-522 protocol, the addition of adjuvant XXXlaparib in patients with residual disease and a germline BRCA mutation is an attractive consideration because it targets a different pathway. The combination of XXXlaparib and pembrolizumab has been studied, and toxicities described are consistent with the profile of the individual drug (\u003cspan\u003e24\u003c/span\u003e). Thus, administration of XXXlaparib, along with standard pembrolizumab, is reasonable in patients with germline BRCA mutations and residual disease after the KEYNOTE-522 regimen.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec13\"\u003e\n \u003ch2\u003eHer2 Positive\u003c/h2\u003e\n \u003cp\u003eThe preferred adjuvant treatment for a casewith stage 1, HER2 positive tumor is TH (Paclitaxel, trastuzumab) as suggested by 85% of S-panel. Forty-two percent of E-panel preferred TH (Paclitaxel, trastuzumab) while 46% voted for TCHP (Docetaxel, carboplatin, trastuzumab, pertuzumab)\u003c/p\u003e\n \u003cp\u003eThe NCCN guidelines has included paclitaxel and trastuzumab as an option for patients with low-risk, HER2-positive, stage 1 tumors. This is based on a trial that studied this combination in 406 patients with small, node negative, HER2 positive tumors. The results showed that the 3-year DFS rate was 98.7% (95% CI, 97.6\u0026ndash;99.8) and the risk of serious toxic effects with this regimen was low with 0.5% incidence of heart failure (\u003cspan\u003e25\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eThe appropriate adjuvant regimen for patients presenting clinically with node negative disease, and who have received TCHP neoadjuvant therapy, and achieved a pCR is trastuzumab as recommended by 63% of S-panel vs. 57% of E-panel. The same percent in both panels (33%) advised for adjuvant Trastuzumab and pertuzumab. Kim et al., found that patients who have received neoadjuvant chemotherapy with dual HER2-blockade, and achieved pCR had an excellent 3-year RFS and results did not differ according to the type of adjuvant anti-HER2 therapy (TP vs T)being 91.7% in TP and 94.2% in T (\u003cspan\u003e26\u003c/span\u003e).\u003c/p\u003e\n \u003cp\u003eBoth panels accepted (57% each) to give adjuvant trastuzumab emtansine to a patient with HER positive breast cancer that has received TCHP neoadjuvant therapy, and at surgery there was residual disease that is HER2 negative.\u003c/p\u003e\n \u003cp\u003eUsing platinum-based treatment for all patients with BRCA1 or BRCA2 mutations who receives neo/adjuvant chemotherapy is accepted by 64% of Egyptian panel and 38% only of ST Gallen panel. Several studies have shown improved pCR rates with incorporation of platinum. However, long-term outcomes remain unknown. So, the routine use of platinum agents as part of\u003c/p\u003e\n \u003cp\u003eneoadjuvant therapy for TNBC is not recommended for most patients, but it may be considered in select patients such as those for whom achieving better local control is necessary. In addition, if platinum agents are included in an anthracycline-based regimen, the optimal sequence of chemotherapy and choice of taxane agent is not established (\u003cspan\u003e27\u003c/span\u003e).\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec14\"\u003e\n \u003ch2\u003eOligometastatic Disease\u003c/h2\u003e\n \u003cp\u003eBoth panels agreed to recommend definitive breast surgery and radiation therapy (E-panel 70%, and S-panel 68%) for a case that had ER-/Her2\u0026thinsp;+\u0026thinsp;tumor, and staging scans revealed a 4 cm tumor, positive axillary, a single pulmonary nodule and she achieved clinical CR with induction THP.\u003c/p\u003e\n \u003cp\u003eIn another patient having stage 2 breast cancer on one side and an isolated contralateral axillary lymph node, the majority of the two panels (84% and 75% of the E- and S-panels, respectively) recommended definitive therapy with curative intent including contralateral axillary surgery and radiation therapy, and adjuvant treatment as standard.\u003c/p\u003e\n\u003c/div\u003e\n\u003cdiv id=\"Sec15\"\u003e\n \u003ch2\u003eMale breast cancer\u003c/h2\u003e\n \u003cp\u003eTamoxifen was endorsed by both panels to be the preferred adjuvant endocrine therapy option for men with breast cancer (Stage 1 excluding minimal risk), ER\u0026thinsp;+\u0026thinsp;HER2 breast cancer (63% and 80% of the E- and S-panels, respectively). However, these percentages dropped to 39%, and 51% for men with stage 3, ER\u0026thinsp;+\u0026thinsp;HER2- breast cancer.\u003c/p\u003e\n\u003c/div\u003e"},{"header":"Discussion","content":"\u003cp\u003eAmong the Egyptian panel, a consensus (\u0026ge;\u0026thinsp;50% approval) was reached in answering 71 out of the 100 questions projected to the panelists. When comparing the answers to these questions by both the E- and the S-panel, was a consensus in answering 82 questions (82%), and no consensus in answering 9 questions. It was difficult to compare answers of the remaining 9 queries since there was no consensus among members of the S-panel themselves.\u003c/p\u003e \u003cp\u003eSo, contrary to the S-panel, E-panel did not recommend using aquapuncture to alleviate symptoms of arthralgia, or neuropathy for patients receiving AI or chemotherapy. They also did not agree to recommend palliative intravaginal estrogens to be given to postmenopausal women.\u003c/p\u003e \u003cp\u003eOn the other hand, Egyptian panelists recommended postoperative radiotherapy for patients who have undergone radical mastectomy for T2 lesions whether they are ER\u0026thinsp;+\u0026thinsp;ve with cancer in one lymph node, or Her2\u0026thinsp;+\u0026thinsp;ve with positive micro or macro metastases in one lymph node, and in TNBC even with micro metastases in one axillary node. The S-panel did not recommend giving postoperative radiotherapy to these patients.\u003c/p\u003e \u003cp\u003eAlso, the E-panel recommended asking for a genomic signature assay for a postmenopausal patient with luminal, grade 2, T1b, N0 breast cancer, and to give such patient adjuvant chemotherapy if proved to have high risk by mamma print assay. St. Gallen panelists did not recommend that. Lastly E-panel, opposite to S-panel, favored adding platinum-based neo/adjuvant chemotherapy to patients with BRCA1 or BRCA2 mutations.\u003c/p\u003e \u003cp\u003eIn our opinion, some of these controversial clinical conditions together with the other 9 situations where there was no consensus even among S-panel are subject to further joint research both on local and international levels.\u003c/p\u003e \u003cp\u003eOne of the important issues that currently face the oncology profession is the financial inability that prevents some of patients from receiving new and costly lines of therapy in most of developing countries and even in low- and middle-income scenarios in developed countries. Many efforts have been made by authorities, international agencies dealing with cancer control, and pharmacy to try lowering drug costs (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eIt is mandatory for each country to develop a national cancer registry to accurately know the number of new cancer cases every year, their specific subtypes, and to define the allocated budget to treat such patients. This would surely help in developing cost effective guidelines for the national payers.\u003c/p\u003e \u003cp\u003eIn addition to these efforts, prevention, and early diagnosis of cases are the main and successful policies to face such a problem and must be a priority for governments specially in developing counties, rather than concentrating on buying expensive drugs even those that are not yet a standard practice and are not reimbursed by insurance companies.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e These guidelines are only a kind of guidance and may not apply to all patients. The best is to choose the proper adjuvant therapies to each case based on many factors such as patient preference, performance status, and physiologic age, tumor characteristics, as well as possible and affordable drugs based on both scientific and economic situations. The key to success is prevention and early diagnosis.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;HK: Conception of the idea and designing the study. Major contribution in writing the manuscript. HK, YW, KM: Collecting the data. HK, SF, MS, ML: Data analysis. HK, YW, KM, SF, MS, ML: Preparing the manuscript. The authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNo fund.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eEthics approval and consent to participate.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the Ethical Committee of the Egyptian National Cancer Institute.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors have no conflict of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003cstrong\u003eAcknowledgement\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCairo University; NCI, medical oncologists\u003c/strong\u003e: Ahmed Magdy Reba, Alfred E. Namour,Hanan E. Shafik,\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHanan R. Nassar, Heba Elzawahry, Hala \u0026nbsp;Aziz, Nasr Allahloubi, Thoraya Abdel Hamid, Yahia M Ismail;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSurgical Oncologists\u003c/strong\u003e: Ahmed Touny; Hatem Aboulkassem, Sharif Abdel Karim, Sherif F. Naguib and\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHoda M. Abdelbaky (\u003cstrong\u003eRadiation Oncology\u003c/strong\u003e), Maha Helal (\u003cstrong\u003eRadiology\u003c/strong\u003e), Nadia Mokhtar (\u003cstrong\u003ePathology\u003c/strong\u003e),\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFaculty of medicine, clinical oncologists:\u0026nbsp;\u003c/strong\u003eAmr Sakr, Emad Hamada, Hanaa Attia, Ibtessam Saadeldin\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eTamer El Nahas, and Omar S. Omar (\u003cstrong\u003eGeneral Surgery\u003c/strong\u003e),\u003cstrong\u003eZagazig University; medical oncologists:\u0026nbsp;\u003c/strong\u003eFoad Abu Taleb, Ola M. Elfararagy, Ahmed A. Alnagar; \u003cstrong\u003eclinical oncologists:\u003c/strong\u003e Abd Emotaleb Mohamed, Maher Aidaros,\u003cstrong\u003eTanta University; clinical oncologists\u003c/strong\u003e: Hanan Shawky, Hesham Tawfik, Lamiss M. Abdel Aziz, \u0026nbsp; Nehal M. Elmashad; \u003cstrong\u003emedical oncologist\u003c/strong\u003e: Hosam EL-Ashtokhy, \u003cstrong\u003eAin Shams University; Clinical oncologists\u003c/strong\u003e: Dina Ahmed Salem, Hesham Elghazaly, Manal M. Abdelwahab,\u003cstrong\u003eAssiut University; clinical oncologists:\u0026nbsp;\u003c/strong\u003eHebatAllah Mahmoud Bakri, Marwa I. Abdelgawad, Samir Eid,\u003cstrong\u003eMilitary medical academy\u003c/strong\u003e; Hany S. Attallah, Hussein Elsayed, Ossama Mohamadin Zein, \u003cstrong\u003eAlexandria University;\u003c/strong\u003e Abdelaziz Belal (\u003cstrong\u003eClinical Oncology, faculty of medicine\u003c/strong\u003e), Nadia A. Abd El Moneim (\u003cstrong\u003eClinical Oncology, Medical Research Institute\u003c/strong\u003e), Ola Sakr (\u003cstrong\u003eConsultant Clinical Oncology\u003c/strong\u003e, \u003cstrong\u003eMedical Research Institute\u003c/strong\u003e),\u003cstrong\u003eMenofia University, clinical oncolgists:\u0026nbsp;\u003c/strong\u003eEman Abdelrazek, Naser Abd El Bary, \u003cstrong\u003eAlazhar University\u003c/strong\u003e; Soheir Saad shaker (\u003cstrong\u003ePathology\u003c/strong\u003e), Wael Eisheshtawy (\u003cstrong\u003eclinical oncology\u003c/strong\u003e),\u003cstrong\u003eMansoura University; medical oncologists\u003c/strong\u003e: Mohamed \u0026nbsp;Aly,Tawfik Elkhodary, \u003cstrong\u003eHelwan University\u003c/strong\u003e; Haytham Abdelkader (\u003cstrong\u003eClinical Oncology\u003c/strong\u003e),\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003ePolice Hospital\u003c/strong\u003e, Gehan El-Shaarany (\u003cstrong\u003eClinical Oncology Consultant\u003c/strong\u003e),\u003cstrong\u003eWadi El Neel Hospital;\u003c/strong\u003e Marwa A. Zaied (\u003cstrong\u003eclinical oncologist\u003c/strong\u003e),\u003cstrong\u003eMaadiArmed Forces Hospital;\u0026nbsp;\u003c/strong\u003eMai Eissa (\u003cstrong\u003eMedical Oncology\u003c/strong\u003e),\u003cstrong\u003eNasser Institute for Research and Treatment\u003c/strong\u003e; Rasha Aboelhassan (Clinical Oncology Consultant).\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eCurigliano G, Burstein HJ, Gnant M, Loibl S, Cameron D, Regan MM, Denkert C, Poortmans P, Weber WP, Th\u0026uuml;rlimann B; Understanding breast cancer complexity to improve patient outcomes: The St Gallen International Consensus Conference for the Primary Therapy of Individuals with Early Breast Cancer 2023.Ann Oncol. 2023 Nov;34(11):970-986\u003c/li\u003e\n\u003cli\u003eKhaled H, Gamal H, Lotayef M, et al. The St. Gallen International Expert Consensus conference on the primary therapy of early breast cancer, 2017: Egyptian view. Breast Cancer Res Treat. 2018;172:545\u0026ndash;50.\u003c/li\u003e\n\u003cli\u003eKhaled H, Nada YW, Ramadan KM, Fekry S, Seleam MS, Gaafar R, Lotayef M. Primary therapy of early breast cancer: Egyptian view of 2021 St. Gallen consensus. J Egypt Natl Canc Inst. 2022 Dec 26;34(1):56.\u003c/li\u003e\n\u003cli\u003eBalic M, Thomssen C, Gnant M, Harbeck N.St. Gallen/Vienna 2023: Optimization of Treatment for Patients with Primary Breast Cancer \u0026ndash; A Brief Summary of the Consensus Discussion. Breast Care (Basel). 2023 Apr;18(3):213-222.\u003c/li\u003e\n\u003cli\u003ehttps://old-prod.asco.org/news-initiatives/policy-news-analysis/updated-position-statement-drug-repository-programs-aims.\u003c/li\u003e\n\u003cli\u003eBecerra-Tomas N, Balducci K, Abar L, Aune D, Cariolou M, Greenwood DC, et al. Postdiagnosis dietary factors, supplement use and breast cancer prognosis: Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis. Int J Cancer. 2023;152(4):616-34.\u003c/li\u003e\n\u003cli\u003ePartridge AH, Niman SM, Ruggeri M, Peccatori FA, Azim HA, Jr., Colleoni M, et al. Who are the women who enrolled in the POSITIVE trial: A global study to support young hormone receptor positive breast cancer survivors desiring pregnancy. Breast. 2021;59:327-38.\u003c/li\u003e\n\u003cli\u003ePagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med 2014;371:107-118.\u003c/li\u003e\n\u003cli\u003eFrancis PA, Regan MM, Fleming GF, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med 2015;372:436-446.\u003c/li\u003e\n\u003cli\u003ehttps://www.nccn.org/guidelines/guidelines-detail?category=1\u0026amp;id=1419.\u003c/li\u003e\n\u003cli\u003ePan H, Gray R, Davies C, et al. Predictors of recurrence during years 5-14 in 46,138 women with ER+ breast cancer allocated 5 years only of endocrine therapy (ET) {Abstract}. J Clin Oncol 34, 2016 (suppl; abstract 505) 2016.\u003c/li\u003e\n\u003cli\u003eSparano J, Gray, RJ, Wood, WC, Makower, DF, Lively, TG, Saphner, TJ et al. TAILORx: Phase III trial of chemoendocrine therapy versus endocrine therapy alone in hormone receptor-positive, HER2-negative, node-negative breast cancer and an intermediate prognosis 21-gene recurrence score [Abstract]. J Clin Oncol 2018;36\u003c/li\u003e\n\u003cli\u003eCardoso F, van\u0026rsquo;t Veer LJ, Bogaerts J, et al. 70-gene signature as an aid to treatment decisions in early-stage breast cancer. New England Journal of Medicine 2016;375:717-729.\u003c/li\u003e\n\u003cli\u003eAlbain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol 2010;11:55-65.\u003c/li\u003e\n\u003cli\u003eLuveta J, Parks RM, Heery DM, Cheung KL. Invasive Lobular Breast Cancer as a Distinct Disease: Implications for Therapeutic Strategy. Oncol Ther (2019) 1\u0026ndash;11. doi: 10.1007/s40487-019-00105-0.\u003c/li\u003e\n\u003cli\u003eLips EH, Mukhtar RA, Yau C, de Ronde JJ, Livasy C, Carey LA, et al. Lobular histology and response to neoadjuvant chemotherapy in invasive breast cancer. Breast Cancer Res Treat (2012) 136(1):34\u0026ndash;43. doi: 10.1007/s10549-012-2233-z.\u003c/li\u003e\n\u003cli\u003eSledge GW, Chagpar A, Perou C. Collective Wisdom: Lobular Carcinoma of the Breast. Am Soc Clin Oncol (2016) 35:18\u0026ndash;21. doi: 10.1200/EDBK_100002.\u003c/li\u003e\n\u003cli\u003eThomas M, Li H, Abraham J, Moore HCF, Budd GT, Montero AJ, et al. Comparison of survival outcomes between treatment with endocrine therapy and chemoendocrine therapy in patients with invasive lobular carcinoma. Cancer Res (2019) 80(4 Suppl):Abstract nr P2-14-13. doi: 10.1158/1538-7445.SABCS19-P2-14-13.\u003c/li\u003e\n\u003cli\u003eConlon N, Ross DS, Howard J, Catalano JP, Dickler MN, Tan LK. Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma? Breast J (2015) 21(5):514\u0026ndash;9. doi: 10.1111/tbj.12445.\u003c/li\u003e\n\u003cli\u003eSanta-Maria C, O\u0026rsquo;Donnell M, Nunes R, et al. Integrating Immunotherapy in Early-Stage Triple-Negative Breast Cancer: Practical Evidence-Based Considerations. J Natl Compr Canc Netw 2022 July; 20(7): 738\u0026ndash;744. doi:10.6004/jnccn.2022.7025.\u003c/li\u003e\n\u003cli\u003eSchmid P, Cortes J, Dent R, et al. Event-free survival with pembrolizumab in early triple-negative breast cancer. N Engl J Med 2022;386:556\u0026ndash;567.\u003c/li\u003e\n\u003cli\u003eSchmid P, Park YH, Ferreira M, et al. KEYNOTE-522: phase 3 study of neoadjuvant pembrolizumab + chemotherapy versus placebo 1 chemo-therapy, followed by adjuvant pembrolizumab versus placebo for early triple-negative breast cancer: pathologic complete response in key subgroups and by treatment exposure and residual cancer burden. Ann Oncol 2019;30(Suppl 5):Abstract 1812.\u003c/li\u003e\n\u003cli\u003eCortazar P, Zhang L, Untch M, et al. Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet 2014;384:164-172.\u003c/li\u003e\n\u003cli\u003eYu EY, Massard C, Retz M, et al. KEYNOTE-365 cohort a: pembrolizumab (pembro) plus olaparib in docetaxel-pretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC) [abstract]. J Clin Oncol 2019;37(Suppl):Abstract 145.\u003c/li\u003e\n\u003cli\u003eTolaney SM, Barry WT, Dang CT, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. N Engl J Med 2015;372:134-141.\u003c/li\u003e\n\u003cli\u003eKim J, Kook Y, Jang J, et al. Adjuvant trastuzumab plus pertuzumab (TP) versus trastuzumab (T) alone in patients achieving pathologic complete response after chemotherapy with TP. Annals of oncology 2022; ABSTRACT 33(7) S614.\u003c/li\u003e\n\u003cli\u003eTutt A, Garber J, Kaufman B, et al. OlympiA Clinical Trial Steering Committee and Investigators. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. N Engl J Med. 2021;384(25):2394-2405.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer, Adjuvant therapy, Egypt","lastPublishedDoi":"10.21203/rs.3.rs-4251493/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4251493/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003ePurpose:\u003c/strong\u003e\u0026nbsp; One of the most important meetings in the field of developing clinical guidelines for early management for breast cancer is the 18\u003csup\u003eth\u003c/sup\u003e St. Gallen International Breast Cancer Conference that was held in March 2023. To tailor these guidelines to suit clinical practice of oncologists in Egypt, an Egyptian Panel were asked to vote on most of the questions of the original St. Gallen consensus.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods\u003c/strong\u003e: The panel consisted of 76 different oncology specialists. 100 questions were assembled and then projected on the monkey survey website. The answers were analyzed in relation to the answers of the St. Gallen panel, 2023.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults and conclusions\u003c/strong\u003e: A consensus (≥ 50% approval) among Egyptian panel was reached in answering 71/100 questions denoting the need of more research tackling different problems in taking care of patients having early breast cancer. Comparing answers of both St. Gallen and Egyptian panel to common questions, no consensus was only in 9 out of the 100 questions. So, St. Gallen recommendations are becoming more and more applicable to most countries even with different levels of income and healthcare scenarios.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"St. Gallen early breast cancer management recommendations are becoming more applicable to most countries even with different levels of income and healthcare scenarios, Egypt as an example","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-04-25 16:28:36","doi":"10.21203/rs.3.rs-4251493/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"385311a6-1180-493c-939f-e430ff630943","owner":[],"postedDate":"April 25th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-05-08T12:15:22+00:00","versionOfRecord":[],"versionCreatedAt":"2024-04-25 16:28:36","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4251493","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4251493","identity":"rs-4251493","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}