Survival in Breast Cancer Patients Compared to Non-Pregnant Controls

Survival in Breast Cancer Patients Compared to Non-Pregnant Controls | 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 Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Survival in Breast Cancer Patients Compared to Non-Pregnant Controls María Martín Cameán, Ibon Jaunarena Marin, Jose Ignacio Sánchez Méndez, and 5 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3901208/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 26 Mar, 2024 Read the published version in Reproductive Biology and Endocrinology → Version 1 posted 7 You are reading this latest preprint version Abstract Background Pregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy. Methods Survival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage. Results Among the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p = 0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p = 0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25). Conclusions The outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype. Breast cancer pregnancy chemotherapy neonatal outcome Figures Figure 1 Figure 2 Figure 3 1. INTRODUCTION The number of women diagnosed with breast cancer during pregnancy has increased recently, in part due to delaying motherhood to older ages ( 1 , 2 ). The treatment of these patients is challenging and requires careful balancing between the treatment of the mother and the safety of the fetus ( 1 , 3 , 4 ). Cancer during pregnancy is a rare entity, with an approximate incidence of 1:1000 pregnancies ( 5 ). Breast cancer is the most frequent type, followed by cervical cancer, lymphoma, ovarian cancer, leukemia, colorectal cancer, and melanoma ( 1 , 6 ). Pregnancy-associated breast cancer (PABC) has been reported to affect 1 in 3000-10,000 pregnancies worldwide, corresponding to approximately 2000–4000 new cases in Europe annually. Pregnancy appears to have 2 opposing effects on the maternal risk of developing breast cancer: a temporal increasing risk during the first years after pregnancy, followed by a long-term protective effect. In fact, PABC is defined as a case that occurs during pregnancy or within a year afterward ( 1 , 2 , 7 , 8 ). More recently, it has been proposed to differentiate cancer associated with pregnancy from cancer diagnosed in the postpartum period, which could extend up to 5–10 years after delivery and which appears to have poorer prognosis ( 1 , 9 , 10 ). Increasingly, however, guided by its epidemiology, some authors consider that the period should be extended to 15 years after childbirth ( 11 ). Given that the safety of treatment during pregnancy has been demonstrated in recent years, the number of patients receiving treatment during pregnancy is increasing ( 12 ). This change has led to fewer pregnancy interruptions and fewer induced premature births. Possible risks are attenuated as pregnancy progresses. Most guidelines recommend chemotherapy treatment during the second and third trimesters, whereas radiotherapy, hormonal, and biological treatments should be delayed until after delivery ( 1 , 13 ). PABC prognosis can be affected by various factors, such as delays in diagnosis and treatment, tumor growth stimulation from pregnancy hormones, and associated immunosuppression ( 1 ). There is evidence suggesting that breast cancer diagnosed during pregnancy and around delivery exhibits more aggressive behavior, including a higher tumor grade, larger size, negative estrogen and progesterone receptor status, HER2 expression, lymphovascular invasion, and lymphocytic infiltration ( 1 , 2 , 11 ). The physiologic gestational changes, such as the increase in plasma volume or glomerular infiltration rate, cause decreased drug concentrations with a potential impact on chemotherapeutic efficacy. There is some disagreement about PABC prognosis, although the latest evidence has shown that the survival of those who received chemotherapy during pregnancy is comparable with non-pregnancy-associated breast cancer ( 9 , 14 ). PABC prognosis has previously been addressed in several studies ( 2 , 5 , 8 , 9 , 13 – 16 ), with considerable controversy around this issue. Some have observed poorer survival among women with PABC ( 2 , 13 , 15 , 17 ). The aim of this study was to estimate the impact of pregnancy on breast cancer prognosis, analyzing the results of a national reference center in order to contribute data to the literature as well as to provide detailed information to patients who will be treated at our center. 2. MATERIALS AND METHODS Study design This was a single-center retrospective case-control study. The study group included patients diagnosed with breast cancer during pregnancy or until 1 year after childbirth, from 2009 to 2021, at La Paz University Hospital, Madrid. Data collected were independent of the outcome of the pregnancy, cancer stage, or treatment received. The control group included young patients (≤40 years) diagnosed with breast cancer without pregnancy 5 years prior to diagnosis at La Paz University Hospital from 2009 to 2021. This study was approved by the La Paz University Hospital ethics committee (version 4.3, 15 Jun 2018, HULP PI-3930). Informed consent was not required due to the retrospective nature of the study, according to ethics committee approval. All patient information was determined by reviewing computerized medical histories. We collected information about demographic data, date of diagnosis, tumor characteristics, surgery, chemotherapy, radiotherapy, endocrine and biologic treatment, and patient outcomes. In the pregnant group, information about the pregnancy was also collected: last menstrual period, type of conception and pregnancy, maternal and fetal complications, treatment received, delivery, newborn weight, arterial pH, Apgar test, and child outcome. All patients included in the study were diagnosed and treated according to the hospital’s protocols and were staged according to the American Joint Committee on Cancer staging system (seventh edition) ( 18 ). Various imaging techniques were used for the diagnosis: ultrasound, mammography, magnetic resonance, and core needle biopsy. All cases were presented to a multidisciplinary committee composed of gynecologists, oncologists, radiotherapists, surgeons, and anatomopathologists. The primary outcome was the difference in overall survival (OS) and disease-free survival (DFS) between patients diagnosed with PABC and patients not diagnosed during pregnancy. OS was defined as time (in months) from cancer diagnosis to death, and disease-free survival (DFS) was defined as time (in months) from cancer diagnosis to locoregional or distant recurrence of disease. The secondary outcome was newborn outcome. Obstetrical and neonatal data were collected: type of conception, complications during pregnancy, congenital malformations, delivery data, gestational age at birth, Apgar test, birth weight, and sex. Statistical analysis Qualitative data were described as absolute frequencies and percentages. Quantitative data were described as mean and standard deviation (SD) if they followed a normal distribution; variables that did not follow a normal distribution were defined as median and interquartile range. The normality of the continuous variables was studied using the Kolmogorov–Smirnov test. The chi-squared test or Fisher's exact test was employed to study the association between categorical variables, and Student's t-test for the association between quantitative variables. The analyses of survival and disease-free time were performed with a Kaplan–Meier analysis calculated from the date of diagnosis to the date of death or recurrence. To compare survival functions by group, log-rank tests were performed. Multivariate Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between pregnancy and OS. The confounding factors under consideration were tumor grade and pathologic stage. All statistical tests were considered bilateral, and P values less than 0.05 were considered significant. The data were analyzed with the IBM SPSS Statistics version 29.0. software package (SPSS, Chicago, IL, USA). 3. RESULTS Among the 89 patients with breast cancer, 34 (38.2%) were diagnosed during pregnancy. Of these, 25 patients were diagnosed with primary breast cancer during any trimester of pregnancy. Seven patients were diagnosed with primary breast cancer within the first year after delivery. In 2 patients, the diagnosis was a recurrence of breast cancer during gestation; one of them was a recurrence in the contralateral breast of a breast cancer she had 4 years earlier, and the other was a lymph node recurrence of a cancer diagnosed one-and-a-half years earlier (Fig. 1 ). The control group included 55 patients diagnosed with breast cancer without any association with pregnancy. All of the patients were younger than 40 years of age at the time of diagnosis (ratio 1:1.62). Demographic features are summarized in Table 1 . Table 1 Demographic Variables Non-pregnant group (N = 55) Pregnant group (N = 34) p-value Variable No. % No. % Delivery 0.049 0 18 52.9 9 33.3 1 7 20.6 15 48.4 ≥2 9 26.5 7 22.6 Smoker 0.003 No 9 52.9 26 92.9 Yes 8 47.1 2 7.1 BRCA 0.157 Normal 6 37.5 10 50 Mutation 10 62.5 6 37.5 Hormonal contraceptive 0.157 No 3 16.7 7 50 Yes 15 62.5 7 50 Median age was 34.88 years (±4.32) for the pregnant group and 33.58 (±4.03) for the control group. The most common histological type in both groups was invasive ductal carcinoma (97.1% in PABC and 85.5% in the control group). Clinicopathologic variables are depicted in Table 2 . Table 2 Clinicopathologic Variables Missing values Non-pregnant Pregnant p-value Non-pregnant Pregnant Variable No. % No. % No. % No. % Pathology 0.369 3 5.5 4 11.8 Unifocal 41 78.8 21 70 Multifocal 11 21.2 9 30 Malignancy Grade 0.023 1 1.8 3 8.8 1 8 14.8 0 2 26 48.1 12 38.7 3 20 37 19 61.3 Molecular 0.148 3 5.5 2 5.9 ER/PR+, Ki67 < 20 13 25 2 6.3 ER/PR+, Ki67≥20 14 26.9 9 28.1 EC/PR+, Ki67≥20,Her2+ 10 19.2 10 50 Her2+ 6 11.5 2 6.3 Triple Negative 9 17.3 9 28.1 Pathologic stage (Grouped) 0.008 4 7.3 0 0,I,II 42 82.4 19 55.9 III,IV 9 17.6 15 44.1 Notes: ER = estrogen receptor. PR = progesterone receptor. HER2 = human epidermal growth factor receptor2. Treatment The type of oncological treatment received is described in Table 3 . Within the PABC group, 8 (25.8%) patients underwent surgery during pregnancy, the majority (50%) of them during the second trimester, 2 in the first, and the other 2 in the third trimester. A total of 16 (48.5%) patients received chemotherapy during pregnancy. The chemotherapy schedule most administered (87.5%) during pregnancy was a combination of an anthracycline (epirubicin) + alkylating agents (cyclophosphamide). It was not until after delivery that taxanes were administered. Among the control group, the chemotherapy regimen most prescribed was anthracycline (epirubicin) + alkylating agents (cyclophosphamide) + 5-fluorouracil + taxanes. Regimens were administered at standard of care dosages. Table 3 Oncological Treatment Missing values Non-pregnant group (N = 55) Pregnant group (N = 34) p-value Non-pregnant Pregnant Variable No. % No. % No. % No. % Breast surgery 0.187 0 1 2.9 None 0 0 2 6.1 Lumpectomy 30 54.5 13 39.4 Mastectomy 20 36.4 14 42.4 Bilateral mastectomy 5 9.1 3 9.1 Quadrantectomy 0 0 1 3 Lymph node surgery 0.487 0 3 8.8 None 1 1.8 2 6.5 SLNB 36 65.5 18 58.1 Lymphadenectomy 18 32.7 11 35.5 Chemotherapy setting 0.070 1 1.8 0 None 9 16.7 2 5.9 Neoadjuvant 35 64.8 19 55.9 Adjuvant 10 18.5 13 38.2 Radiotherapy 0.189 0 0 None 11 20 11 32.4 Yes 44 80 23 67.6 Endocrine Therapy 0.692 1 1.8 4 11.8 None 15 27.8 11 36.7 Tamoxifen 28 51.9 14 46.7 Aromatase inhibitor 11 20.4 5 16.7 Abbreviations: SLNB = sentinel lymph node biopsy. Survival Median follow-up was 47 months for the pregnant group and 46 months for the control group. During follow-up, 11 (33.3%) patients in the PABC group and 5 (9.1%) in the control group died. The observed 5-year OS for the pregnant and control group was 65.0% and 87.6%, respectively. The median survival time was 6 years for the study group and 7 years for the control group (Fig. 2 ). Figure 3 shows the results obtained for the observed 5-year DFS for both groups; 85.3% for the pregnant group and 91% for the nonpregnant group. These differences were not statistically significant (log rank: 0.13). After adjustments for tumor grade and pathologic stage, we found no evidence of poorer prognosis for women diagnosed with PABC regarding OS (HR 2.03; 95% CI 0.61 to 6.79; P = 0.25) Obstetrics and neonatal outcome Data from 34 pregnancies were collected. Data from 2 were excluded: one was a first-trimester miscarriage and the other was a terminated pregnancy. Two of the remaining 32 pregnancies were twins, both of them bicorial biamniotic. Thirty (93.8%) pregnancies were naturally conceived, and 2 (6.3%) by in vitro fertilization. Chemotherapy was administered during 15 (45.4%) pregnancies, and 8 (24.2%) patients underwent surgery during pregnancy. Most (82.1%) of the pregnant women did not suffer any complication. Minor complications were reported: 1 diet-controlled gestational diabetes, 1 preeclampsia, 1 small for gestational age, 1 abnormal placentation (placenta previa), and 1 threatened preterm labor (which ended in full-term delivery). Only 2 patients received any treatment different from the oncologic one: tocolytic treatment and prophylactic acetylsalicylic acid. Eight (29.6%) patients had a spontaneous delivery. Eleven (40.7%) deliveries were induced, 75% of which were due to oncologic causes (treatment organization). Cesarean section was scheduled for 8 (29.6%) patients. Most (51.9%) had a vaginal delivery, 44.4% ended in cesarean section, and there was only 1 instrumental delivery (vacuum). A total of 34 children (including 2 pairs of twins) were born from 32 mothers diagnosed with PABC. Average birth weight was 2819 gr (±488). The number and type of congenital malformations were similar to those in the general population; 1 was diagnosed with bilateral cryptorchidism and 1 with testicular hydrocele. 4. DISCUSSION The most remarkable finding from this study is the difference in prognosis between the groups: 33.3% died in the pregnant group vs 9.1% in the control group, with a statistically significant shorter OS in the pregnant group. However, after adjustment for tumor characteristics (grade and pathologic stage), these associations were attenuated. These findings support previous studies ( 2 , 5 , 11 , 13 , 14 , 16 ) that suggested pregnancy-related breast cancer is more likely to be larger tumors, higher stage, more poorly differentiated, and with a higher frequency of lymph node metastases. In agreement with the literature, in this study we found different tumor characteristics when comparing the groups, with PABC showing a more aggressive profile. In the pregnant group there was a higher prevalence of triple-negative tumor, poorer differentiation, and diagnosis in more advanced stages compared with the non-pregnant group. Several explanations have been proposed for the poorer prognosis of pregnancy-related breast cancer. One is delayed diagnosis, which can occur in pregnant women because palpable masses or lumps can be ascribed to normal breast changes during pregnancy. To prevent this, any mass during pregnancy or postpartum should be evaluated promptly. The mechanisms driving PABC remain unclear, and many hypotheses have been postulated. During pregnancy, elevated levels of estrogen, progesterone, and insulin growth factor induce breast cell proliferation and could initiate tumorigenesis or stimulate growth of cells that have already undergone malignant transformation. However, the majority of PABC does not express hormonal receptors. In xenograft models of PABC it has been shown that, although lacking hormonal expression, systemic estrogens are needed for their formation and the progression of ER-negative cancers ( 11 ). Another factor that influences the development of PABC is the combination of immunosuppression associated with pregnancy, immune tolerance, and inflammatory changes related to mammary gland involution ( 9 – 11 ). Due to the poorer PABC prognosis, an increased awareness among clinicians and patients could help achieve earlier diagnoses. We suggest including breast screening as part of the pregnancy visit protocol, either with breast exploration or with imaging tests. Previous studies have suggested that ultrasound and mammography with fetal shielding are both appropriate diagnostic tools with no fetal risk ( 9 , 16 ). PABC prognosis has previously been addressed in several studies, with considerable controversy around this issue. A meta-analysis including 3628 cases and 37,100 controls showed a significantly higher risk of death in PABC compared with those not pregnant (pHR: 1.44; 95% CI [1.27–1.63]). However, this difference was only statistically significant in the group diagnosed postpartum (pHR: 1.84; 95% CI [1.28–2.65]) and not in the group diagnosed during pregnancy (pHR: 1.29; 95% CI [0.74–2.24]) ( 15 ). The study by Viuff et al. ( 13 ) found higher overall mortality among women with PABC in the first 2 years after diagnosis compared with non-pregnant women with breast cancer, including 156 and 11,110 patients, respectively (HR 2.28 [1.48–3.52)]. In contrast, survival was comparable between the groups from 2 years after diagnosis. A later study by Amant et al. ( 14 ), which included 311 women with PABC compared with 865 women with breast cancer who were not pregnant, found similar OS in both groups. Nevertheless, regarding the DFS analysis, although the HR 1.34 result (95% CI; 0.93–1.91) suggests better outcomes for the nonpregnant group, it is not conclusive. An ampliation of this study focused on a subgroup of patients who received chemotherapy during pregnancy, comparing the prognosis between PABC treated with standard chemotherapy regimens and a non-pregnant control group ( 9 ). Although comparable results were reported in terms of DFS and OS, a poorer OS was suggested for pregnant women receiving chemotherapy for luminal A breast cancer. PABC treatment is challenging for clinicians, patients, and their families, because it requires careful balancing between the treatment of the mother and the safety of the fetus. Guidelines recommend following the same treatment that is standard for non-pregnant patients. Following this recommendation, no differences were observed in our study between the study and control groups in the treatment received, the only exception being that taxane-based chemotherapy and radiotherapy was delayed until birth, following the standard recommendations at the time of these patients’ diagnosis. Breast cancer surgery can be performed safely during any stage of pregnancy ( 1 ). Chemotherapy, in a neoadjuvant or adjuvant setting, including anthracyclines, fluoropyrimidines, taxanes, and platinum derivates, is feasible after 12 weeks of pregnancy ( 1 , 5 , 19 ). However, hormonal therapy is not recommended during pregnancy and should be delayed until birth ( 20 ), and trastuzumab is also contraindicated during pregnancy ( 21 ). Radiotherapy is possible during the first half of pregnancy ( 1 ). Despite prenatal exposure to maternal cancer, the associated maternal distress, diagnostic procedures, and oncological treatment including chemotherapy, the outcome for children in our study did not differ from that of the general population, in line with previous literature. Normal behavioral competence and cognitive and cardiac outcomes have been reported in children up to 18 years of age for fetuses exposed to chemotherapy in utero ( 22 – 25 ). There are some limitations to this study that must be taken into account. This was a single-center study which, added to the rarity of this entity, resulted in a small sample size; therefore, it achieved insufficient power in the statistical analysis. Also, due to small size of the groups, it was not possible to analyze the results by the subgroup of patients diagnosed during pregnancy and during the postpartum period. 5. CONCLUSIONS In our cohort of patients, we found poorer survival in those diagnosed with breast cancer during pregnancy or at 1 year postpartum when compared with nonpregnant patients with breast cancer, as a consequence of a more aggressive PABC phenotype. The group with PABC also had a more advanced stage and the cancer was more poorly differentiated than in controls. After adjustment for tumor characteristics, these findings disappeared. Increased awareness among patients and specialists could help achieve earlier diagnoses. Among patients with PABC, no higher rate of obstetric or neonatal complication was identified than that in the general population. Declarations Ethics approval and consent to participate: This study was approved by the La Paz University Hospital ethics committee (version 4.3, 15 Jun 2018, HULP PI-3930). Consent for publication: Not applicable Availability of data and materials: All data generated or analysed during this study are included in this published article. Competing interests: The authors declare that they have no competing interests Funding: There has been no financial support for this work. Authors' contributions: AHG and IZ conceived and designed the original study, provided guidance, supervision and revision of the article. MMC collected and analyzed clinical data and drafted the manuscript. IJM analyzed the data. JISM, CMA, EMB collected clinical data. FBA provided guidance and revision of the article. All authors read and approved the final manuscript. Acknowledgements: Not aplicable. References Boere I, Lok C, Poortmans P, Koppert L, Painter R, vd Heuvel-Eibrink MM, et al. Breast cancer during pregnancy: epidemiology, phenotypes, presentation during pregnancy and therapeutic modalities. Best Pract Res Clin Obstet Gynaecol [Internet]. 2022;82:46–59. 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Cite Share Download PDF Status: Published Journal Publication published 26 Mar, 2024 Read the published version in Reproductive Biology and Endocrinology → Version 1 posted Editorial decision: Revision requested 12 Feb, 2024 Reviews received at journal 10 Feb, 2024 Reviewers agreed at journal 03 Feb, 2024 Reviewers invited by journal 01 Feb, 2024 Editor assigned by journal 30 Jan, 2024 Submission checks completed at journal 30 Jan, 2024 First submitted to journal 26 Jan, 2024 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. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies 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-3901208","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":270152593,"identity":"08afc32a-4019-4693-a64e-f6f859001543","order_by":0,"name":"María Martín Cameán","email":"data:image/png;base64,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","orcid":"","institution":"La Paz University Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"María","middleName":"Martín","lastName":"Cameán","suffix":""},{"id":270152595,"identity":"4a00a292-7ce1-415c-8242-d5d56cc4ec64","order_by":1,"name":"Ibon Jaunarena Marin","email":"","orcid":"","institution":"Donostia University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ibon","middleName":"Jaunarena","lastName":"Marin","suffix":""},{"id":270152596,"identity":"f4ae4070-b993-4626-abeb-3e63198817b0","order_by":2,"name":"Jose Ignacio Sánchez Méndez","email":"","orcid":"","institution":"La Paz University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jose","middleName":"Ignacio Sánchez","lastName":"Méndez","suffix":""},{"id":270152597,"identity":"4d2f664b-4b0d-47c4-91d9-1cd29484df74","order_by":3,"name":"Covadonga Martí Alvarez","email":"","orcid":"","institution":"La Paz University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Covadonga","middleName":"Martí","lastName":"Alvarez","suffix":""},{"id":270152598,"identity":"8326606b-352e-4013-912b-e13b2ddd8613","order_by":4,"name":"Félix Boria Alegre","email":"","orcid":"","institution":"Clínica Universidad de Navarra","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Félix","middleName":"Boria","lastName":"Alegre","suffix":""},{"id":270152600,"identity":"11ab509c-63db-4679-b7b9-43a8303894bd","order_by":5,"name":"Elena Martín Boado","email":"","orcid":"","institution":"La Paz University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Elena","middleName":"Martín","lastName":"Boado","suffix":""},{"id":270152601,"identity":"e49678f4-8d8a-4555-bfc0-21220069aeee","order_by":6,"name":"Ignacio Zapardiel","email":"","orcid":"","institution":"La Paz University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Ignacio","middleName":"","lastName":"Zapardiel","suffix":""},{"id":270152602,"identity":"cb5ea656-8e24-47bf-8003-90f60b5a885a","order_by":7,"name":"Alicia Hernández Gutiérrez","email":"","orcid":"","institution":"La Paz University Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Alicia","middleName":"Hernández","lastName":"Gutiérrez","suffix":""}],"badges":[],"createdAt":"2024-01-26 22:29:14","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3901208/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3901208/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12958-024-01206-w","type":"published","date":"2024-03-26T15:01:45+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":50510370,"identity":"e3ef2988-b816-47c3-8481-8c6e82d19fb8","added_by":"auto","created_at":"2024-02-01 16:04:21","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":19465,"visible":true,"origin":"","legend":"\u003cp\u003eLegend not included with this version\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-3901208/v1/dd4f8b05fcf131730e9bbf43.png"},{"id":50510369,"identity":"d5965939-4ba8-426d-880c-a908c2d81545","added_by":"auto","created_at":"2024-02-01 16:04:21","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":45351,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves for \u003cstrong\u003eOverall Survival (OS)\u003c/strong\u003efor the pregnant and nonpregnant groups. \u003cstrong\u003eLog Rank: 0.02\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-3901208/v1/16df321550b9273cb11e9898.png"},{"id":50510371,"identity":"aa167030-bd9a-49e4-87aa-203a540b8a16","added_by":"auto","created_at":"2024-02-01 16:04:21","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":29883,"visible":true,"origin":"","legend":"\u003cp\u003eKaplan-Meier curves for \u003cstrong\u003eDisease Free Survival (DFS)\u003c/strong\u003e for the pregnant and nonpregnant groups. \u003cstrong\u003eLog Rank:0.13\u003c/strong\u003e\u003c/p\u003e","description":"","filename":"3.png","url":"https://assets-eu.researchsquare.com/files/rs-3901208/v1/649b722e284e3157aa3ec95f.png"},{"id":53869981,"identity":"b97fdc19-67a9-454c-b458-642912cd1bf7","added_by":"auto","created_at":"2024-04-01 15:12:40","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":406716,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3901208/v1/1bdfd0a8-ca24-4ae5-94b1-b06c40372aac.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"\u003cp\u003eSurvival in Breast Cancer Patients Compared to Non-Pregnant Controls\u003c/p\u003e","fulltext":[{"header":"1. INTRODUCTION","content":"\u003cp\u003eThe number of women diagnosed with breast cancer during pregnancy has increased recently, in part due to delaying motherhood to older ages (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The treatment of these patients is challenging and requires careful balancing between the treatment of the mother and the safety of the fetus (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eCancer during pregnancy is a rare entity, with an approximate incidence of 1:1000 pregnancies (\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). Breast cancer is the most frequent type, followed by cervical cancer, lymphoma, ovarian cancer, leukemia, colorectal cancer, and melanoma (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). Pregnancy-associated breast cancer (PABC) has been reported to affect 1 in 3000-10,000 pregnancies worldwide, corresponding to approximately 2000\u0026ndash;4000 new cases in Europe annually.\u003c/p\u003e \u003cp\u003ePregnancy appears to have 2 opposing effects on the maternal risk of developing breast cancer: a temporal increasing risk during the first years after pregnancy, followed by a long-term protective effect. In fact, PABC is defined as a case that occurs during pregnancy or within a year afterward (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e). More recently, it has been proposed to differentiate cancer associated with pregnancy from cancer diagnosed in the postpartum period, which could extend up to 5\u0026ndash;10 years after delivery and which appears to have poorer prognosis (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). Increasingly, however, guided by its epidemiology, some authors consider that the period should be extended to 15 years after childbirth (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eGiven that the safety of treatment during pregnancy has been demonstrated in recent years, the number of patients receiving treatment during pregnancy is increasing (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). This change has led to fewer pregnancy interruptions and fewer induced premature births. Possible risks are attenuated as pregnancy progresses. Most guidelines recommend chemotherapy treatment during the second and third trimesters, whereas radiotherapy, hormonal, and biological treatments should be delayed until after delivery (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e). PABC prognosis can be affected by various factors, such as delays in diagnosis and treatment, tumor growth stimulation from pregnancy hormones, and associated immunosuppression (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere is evidence suggesting that breast cancer diagnosed during pregnancy and around delivery exhibits more aggressive behavior, including a higher tumor grade, larger size, negative estrogen and progesterone receptor status, HER2 expression, lymphovascular invasion, and lymphocytic infiltration (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe physiologic gestational changes, such as the increase in plasma volume or glomerular infiltration rate, cause decreased drug concentrations with a potential impact on chemotherapeutic efficacy. There is some disagreement about PABC prognosis, although the latest evidence has shown that the survival of those who received chemotherapy during pregnancy is comparable with non-pregnancy-associated breast cancer (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePABC prognosis has previously been addressed in several studies (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan additionalcitationids=\"CR14 CR15\" citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e), with considerable controversy around this issue. Some have observed poorer survival among women with PABC (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e). The aim of this study was to estimate the impact of pregnancy on breast cancer prognosis, analyzing the results of a national reference center in order to contribute data to the literature as well as to provide detailed information to patients who will be treated at our center.\u003c/p\u003e"},{"header":"2. MATERIALS AND METHODS","content":"\u003cp\u003e \u003cb\u003eStudy design\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThis was a single-center retrospective case-control study. The study group included patients diagnosed with breast cancer during pregnancy or until 1 year after childbirth, from 2009 to 2021, at La Paz University Hospital, Madrid. Data collected were independent of the outcome of the pregnancy, cancer stage, or treatment received. The control group included young patients (\u0026le;40 years) diagnosed with breast cancer without pregnancy 5 years prior to diagnosis at La Paz University Hospital from 2009 to 2021.\u003c/p\u003e \u003cp\u003eThis study was approved by the La Paz University Hospital ethics committee (version 4.3, 15 Jun 2018, HULP PI-3930). Informed consent was not required due to the retrospective nature of the study, according to ethics committee approval.\u003c/p\u003e \u003cp\u003eAll patient information was determined by reviewing computerized medical histories. We collected information about demographic data, date of diagnosis, tumor characteristics, surgery, chemotherapy, radiotherapy, endocrine and biologic treatment, and patient outcomes. In the pregnant group, information about the pregnancy was also collected: last menstrual period, type of conception and pregnancy, maternal and fetal complications, treatment received, delivery, newborn weight, arterial pH, Apgar test, and child outcome.\u003c/p\u003e \u003cp\u003eAll patients included in the study were diagnosed and treated according to the hospital\u0026rsquo;s protocols and were staged according to the American Joint Committee on Cancer staging system (seventh edition) (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Various imaging techniques were used for the diagnosis: ultrasound, mammography, magnetic resonance, and core needle biopsy. All cases were presented to a multidisciplinary committee composed of gynecologists, oncologists, radiotherapists, surgeons, and anatomopathologists.\u003c/p\u003e \u003cp\u003eThe primary outcome was the difference in overall survival (OS) and disease-free survival (DFS) between patients diagnosed with PABC and patients not diagnosed during pregnancy. OS was defined as time (in months) from cancer diagnosis to death, and disease-free survival (DFS) was defined as time (in months) from cancer diagnosis to locoregional or distant recurrence of disease.\u003c/p\u003e \u003cp\u003eThe secondary outcome was newborn outcome. Obstetrical and neonatal data were collected: type of conception, complications during pregnancy, congenital malformations, delivery data, gestational age at birth, Apgar test, birth weight, and sex.\u003c/p\u003e \u003cp\u003e \u003cb\u003eStatistical analysis\u003c/b\u003e \u003c/p\u003e \u003cp\u003eQualitative data were described as absolute frequencies and percentages. Quantitative data were described as mean and standard deviation (SD) if they followed a normal distribution; variables that did not follow a normal distribution were defined as median and interquartile range.\u003c/p\u003e \u003cp\u003eThe normality of the continuous variables was studied using the Kolmogorov\u0026ndash;Smirnov test. The chi-squared test or Fisher's exact test was employed to study the association between categorical variables, and Student's t-test for the association between quantitative variables.\u003c/p\u003e \u003cp\u003eThe analyses of survival and disease-free time were performed with a Kaplan\u0026ndash;Meier analysis calculated from the date of diagnosis to the date of death or recurrence. To compare survival functions by group, log-rank tests were performed.\u003c/p\u003e \u003cp\u003eMultivariate Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of the association between pregnancy and OS. The confounding factors under consideration were tumor grade and pathologic stage.\u003c/p\u003e \u003cp\u003eAll statistical tests were considered bilateral, and P values less than 0.05 were considered significant. The data were analyzed with the IBM SPSS Statistics version 29.0. software package (SPSS, Chicago, IL, USA).\u003c/p\u003e"},{"header":"3. RESULTS","content":"\u003cp\u003eAmong the 89 patients with breast cancer, 34 (38.2%) were diagnosed during pregnancy. Of these, 25 patients were diagnosed with primary breast cancer during any trimester of pregnancy. Seven patients were diagnosed with primary breast cancer within the first year after delivery. In 2 patients, the diagnosis was a recurrence of breast cancer during gestation; one of them was a recurrence in the contralateral breast of a breast cancer she had 4 years earlier, and the other was a lymph node recurrence of a cancer diagnosed one-and-a-half years earlier (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThe control group included 55 patients diagnosed with breast cancer without any association with pregnancy. All of the patients were younger than 40 years of age at the time of diagnosis (ratio 1:1.62). Demographic features are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic Variables\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNon-pregnant group\u003c/span\u003e\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePregnant group\u003c/span\u003e\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e 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\u003cp\u003e\u003cb\u003e0.049\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e48.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e22.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmoker\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.003\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e92.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBRCA\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.157\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNormal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMutation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e37.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eHormonal contraceptive\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.157\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e62.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eMedian age was 34.88 years (\u0026plusmn;4.32) for the pregnant group and 33.58 (\u0026plusmn;4.03) for the control group. The most common histological type in both groups was invasive ductal carcinoma (97.1% in PABC and 85.5% in the control group). Clinicopathologic variables are depicted in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinicopathologic Variables\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e \u003cp\u003eMissing values\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNon-pregnant\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePregnant\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNon-pregnant\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePregnant\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathology\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.369\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e11.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnifocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e78.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMultifocal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMalignancy Grade\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.023\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e8.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e61.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMolecular\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.148\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e5.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eER/PR+, Ki67\u0026thinsp;\u0026lt;\u0026thinsp;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eER/PR+, Ki67\u0026ge;20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEC/PR+, Ki67\u0026ge;20,Her2+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHer2+\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTriple Negative\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e28.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003ePathologic stage (Grouped)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cb\u003e0.008\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e7.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e0,I,II\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e82.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIII,IV\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e44.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"10\" nameend=\"c10\" namest=\"c1\"\u003e \u003cp\u003eNotes: ER\u0026thinsp;=\u0026thinsp;estrogen receptor. PR\u0026thinsp;=\u0026thinsp;progesterone receptor. HER2\u0026thinsp;=\u0026thinsp;human epidermal growth factor receptor2.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eTreatment\u003c/b\u003e \u003c/p\u003e \u003cp\u003eThe type of oncological treatment received is described in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. Within the PABC group, 8 (25.8%) patients underwent surgery during pregnancy, the majority (50%) of them during the second trimester, 2 in the first, and the other 2 in the third trimester. A total of 16 (48.5%) patients received chemotherapy during pregnancy. The chemotherapy schedule most administered (87.5%) during pregnancy was a combination of an anthracycline (epirubicin)\u0026thinsp;+\u0026thinsp;alkylating agents (cyclophosphamide). It was not until after delivery that taxanes were administered. Among the control group, the chemotherapy regimen most prescribed was anthracycline (epirubicin)\u0026thinsp;+\u0026thinsp;alkylating agents (cyclophosphamide)\u0026thinsp;+\u0026thinsp;5-fluorouracil\u0026thinsp;+\u0026thinsp;taxanes. Regimens were administered at standard of care dosages.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eOncological Treatment\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"10\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c10\" colnum=\"10\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"4\" nameend=\"c10\" namest=\"c7\"\u003e \u003cp\u003eMissing values\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNon-pregnant group\u003c/span\u003e\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;55)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePregnant group\u003c/span\u003e\u003c/p\u003e \u003cp\u003e(N\u0026thinsp;=\u0026thinsp;34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003ep-value\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003eNon-pregnant\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c10\" namest=\"c9\"\u003e \u003cp\u003e\u003cspan type=\"Underline\" class=\"Underline\" name=\"Emphasis\"\u003ePregnant\u003c/span\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003eNo.\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e%\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eBreast surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.187\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLumpectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e39.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMastectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e42.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBilateral mastectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eQuadrantectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eLymph node surgery\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.487\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e8.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSLNB\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e65.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e58.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphadenectomy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e32.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e35.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eChemotherapy setting\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.070\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeoadjuvant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e64.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdjuvant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e13\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eRadiotherapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.189\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e32.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e67.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEndocrine Therapy\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.692\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e1.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e \u003cp\u003e11.8\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e36.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTamoxifen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e51.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e46.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAromatase inhibitor\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c10\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"10\" nameend=\"c10\" namest=\"c1\"\u003e \u003cp\u003eAbbreviations: SLNB\u0026thinsp;=\u0026thinsp;sentinel lymph node biopsy.\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cb\u003eSurvival\u003c/b\u003e \u003c/p\u003e \u003cp\u003eMedian follow-up was 47 months for the pregnant group and 46 months for the control group. During follow-up, 11 (33.3%) patients in the PABC group and 5 (9.1%) in the control group died. The observed 5-year OS for the pregnant and control group was 65.0% and 87.6%, respectively. The median survival time was 6 years for the study group and 7 years for the control group (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eFigure \u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows the results obtained for the observed 5-year DFS for both groups; 85.3% for the pregnant group and 91% for the nonpregnant group. These differences were not statistically significant (log rank: 0.13).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eAfter adjustments for tumor grade and pathologic stage, we found no evidence of poorer prognosis for women diagnosed with PABC regarding OS (HR 2.03; 95% CI 0.61 to 6.79; P\u0026thinsp;=\u0026thinsp;0.25)\u003c/p\u003e \u003cp\u003e \u003cb\u003eObstetrics and neonatal outcome\u003c/b\u003e \u003c/p\u003e \u003cp\u003eData from 34 pregnancies were collected. Data from 2 were excluded: one was a first-trimester miscarriage and the other was a terminated pregnancy. Two of the remaining 32 pregnancies were twins, both of them bicorial biamniotic. Thirty (93.8%) pregnancies were naturally conceived, and 2 (6.3%) by \u003cem\u003ein vitro\u003c/em\u003e fertilization. Chemotherapy was administered during 15 (45.4%) pregnancies, and 8 (24.2%) patients underwent surgery during pregnancy. Most (82.1%) of the pregnant women did not suffer any complication. Minor complications were reported: 1 diet-controlled gestational diabetes, 1 preeclampsia, 1 small for gestational age, 1 abnormal placentation (placenta previa), and 1 threatened preterm labor (which ended in full-term delivery). Only 2 patients received any treatment different from the oncologic one: tocolytic treatment and prophylactic acetylsalicylic acid. Eight (29.6%) patients had a spontaneous delivery. Eleven (40.7%) deliveries were induced, 75% of which were due to oncologic causes (treatment organization). Cesarean section was scheduled for 8 (29.6%) patients. Most (51.9%) had a vaginal delivery, 44.4% ended in cesarean section, and there was only 1 instrumental delivery (vacuum).\u003c/p\u003e \u003cp\u003eA total of 34 children (including 2 pairs of twins) were born from 32 mothers diagnosed with PABC. Average birth weight was 2819 gr (\u0026plusmn;488). The number and type of congenital malformations were similar to those in the general population; 1 was diagnosed with bilateral cryptorchidism and 1 with testicular hydrocele.\u003c/p\u003e"},{"header":"4. DISCUSSION","content":"\u003cp\u003eThe most remarkable finding from this study is the difference in prognosis between the groups: 33.3% died in the pregnant group vs 9.1% in the control group, with a statistically significant shorter OS in the pregnant group. However, after adjustment for tumor characteristics (grade and pathologic stage), these associations were attenuated. These findings support previous studies (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) that suggested pregnancy-related breast cancer is more likely to be larger tumors, higher stage, more poorly differentiated, and with a higher frequency of lymph node metastases. In agreement with the literature, in this study we found different tumor characteristics when comparing the groups, with PABC showing a more aggressive profile. In the pregnant group there was a higher prevalence of triple-negative tumor, poorer differentiation, and diagnosis in more advanced stages compared with the non-pregnant group.\u003c/p\u003e \u003cp\u003eSeveral explanations have been proposed for the poorer prognosis of pregnancy-related breast cancer. One is delayed diagnosis, which can occur in pregnant women because palpable masses or lumps can be ascribed to normal breast changes during pregnancy. To prevent this, any mass during pregnancy or postpartum should be evaluated promptly.\u003c/p\u003e \u003cp\u003eThe mechanisms driving PABC remain unclear, and many hypotheses have been postulated. During pregnancy, elevated levels of estrogen, progesterone, and insulin growth factor induce breast cell proliferation and could initiate tumorigenesis or stimulate growth of cells that have already undergone malignant transformation. However, the majority of PABC does not express hormonal receptors. In xenograft models of PABC it has been shown that, although lacking hormonal expression, systemic estrogens are needed for their formation and the progression of ER-negative cancers (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Another factor that influences the development of PABC is the combination of immunosuppression associated with pregnancy, immune tolerance, and inflammatory changes related to mammary gland involution (\u003cspan additionalcitationids=\"CR10\" citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDue to the poorer PABC prognosis, an increased awareness among clinicians and patients could help achieve earlier diagnoses. We suggest including breast screening as part of the pregnancy visit protocol, either with breast exploration or with imaging tests. Previous studies have suggested that ultrasound and mammography with fetal shielding are both appropriate diagnostic tools with no fetal risk (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e \u003cp\u003ePABC prognosis has previously been addressed in several studies, with considerable controversy around this issue. A meta-analysis including 3628 cases and 37,100 controls showed a significantly higher risk of death in PABC compared with those not pregnant (pHR: 1.44; 95% CI [1.27\u0026ndash;1.63]). However, this difference was only statistically significant in the group diagnosed postpartum (pHR: 1.84; 95% CI [1.28\u0026ndash;2.65]) and not in the group diagnosed during pregnancy (pHR: 1.29; 95% CI [0.74\u0026ndash;2.24]) (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). The study by Viuff et al. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) found higher overall mortality among women with PABC in the first 2 years after diagnosis compared with non-pregnant women with breast cancer, including 156 and 11,110 patients, respectively (HR 2.28 [1.48\u0026ndash;3.52)]. In contrast, survival was comparable between the groups from 2 years after diagnosis.\u003c/p\u003e \u003cp\u003eA later study by Amant et al. (\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e), which included 311 women with PABC compared with 865 women with breast cancer who were not pregnant, found similar OS in both groups. Nevertheless, regarding the DFS analysis, although the HR 1.34 result (95% CI; 0.93\u0026ndash;1.91) suggests better outcomes for the nonpregnant group, it is not conclusive. An ampliation of this study focused on a subgroup of patients who received chemotherapy during pregnancy, comparing the prognosis between PABC treated with standard chemotherapy regimens and a non-pregnant control group (\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e). Although comparable results were reported in terms of DFS and OS, a poorer OS was suggested for pregnant women receiving chemotherapy for luminal A breast cancer.\u003c/p\u003e \u003cp\u003ePABC treatment is challenging for clinicians, patients, and their families, because it requires careful balancing between the treatment of the mother and the safety of the fetus. Guidelines recommend following the same treatment that is standard for non-pregnant patients. Following this recommendation, no differences were observed in our study between the study and control groups in the treatment received, the only exception being that taxane-based chemotherapy and radiotherapy was delayed until birth, following the standard recommendations at the time of these patients\u0026rsquo; diagnosis. Breast cancer surgery can be performed safely during any stage of pregnancy (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e). Chemotherapy, in a neoadjuvant or adjuvant setting, including anthracyclines, fluoropyrimidines, taxanes, and platinum derivates, is feasible after 12 weeks of pregnancy (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). However, hormonal therapy is not recommended during pregnancy and should be delayed until birth (\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e), and trastuzumab is also contraindicated during pregnancy (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Radiotherapy is possible during the first half of pregnancy (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eDespite prenatal exposure to maternal cancer, the associated maternal distress, diagnostic procedures, and oncological treatment including chemotherapy, the outcome for children in our study did not differ from that of the general population, in line with previous literature. Normal behavioral competence and cognitive and cardiac outcomes have been reported in children up to 18 years of age for fetuses exposed to chemotherapy \u003cem\u003ein utero\u003c/em\u003e (\u003cspan additionalcitationids=\"CR23 CR24\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e).\u003c/p\u003e \u003cp\u003eThere are some limitations to this study that must be taken into account. This was a single-center study which, added to the rarity of this entity, resulted in a small sample size; therefore, it achieved insufficient power in the statistical analysis. Also, due to small size of the groups, it was not possible to analyze the results by the subgroup of patients diagnosed during pregnancy and during the postpartum period.\u003c/p\u003e"},{"header":"5. CONCLUSIONS","content":"\u003cp\u003eIn our cohort of patients, we found poorer survival in those diagnosed with breast cancer during pregnancy or at 1 year postpartum when compared with nonpregnant patients with breast cancer, as a consequence of a more aggressive PABC phenotype. The group with PABC also had a more advanced stage and the cancer was more poorly differentiated than in controls. After adjustment for tumor characteristics, these findings disappeared. Increased awareness among patients and specialists could help achieve earlier diagnoses. Among patients with PABC, no higher rate of obstetric or neonatal complication was identified than that in the general population.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate: This study was approved by the La Paz University Hospital ethics committee (version 4.3, 15 Jun 2018, HULP PI-3930).\u003c/p\u003e\n\u003cp\u003eConsent for publication:\u0026nbsp;Not applicable\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials: All data generated or analysed during this study are included in this published article.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eCompeting interests: The authors declare that they have no competing interests\u003c/p\u003e\n\u003cp\u003eFunding: There has been no financial support for this work.\u003c/p\u003e\n\u003cp\u003eAuthors\u0026apos; contributions: \u0026nbsp;AHG and IZ conceived and designed the original study, provided guidance, supervision and revision of the article. MMC collected and analyzed clinical data and drafted the manuscript. IJM analyzed the data. JISM, CMA, EMB collected clinical data. FBA provided guidance and revision of the article. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgements: Not aplicable. \u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBoere I, Lok C, Poortmans P, Koppert L, Painter R, vd Heuvel-Eibrink MM, et al. Breast cancer during pregnancy: epidemiology, phenotypes, presentation during pregnancy and therapeutic modalities. Best Pract Res Clin Obstet Gynaecol [Internet]. 2022;82:46\u0026ndash;59. Available from: https://doi.org/10.1016/j.bpobgyn.2022.05.001\u003c/li\u003e\n\u003cli\u003eJohansson ALV, Andersson TML, Hsieh CC, Jirstr\u0026ouml;m K, Cnattingius S, Fredriksson I, et al. Tumor characteristics and prognosis in women with pregnancy-associated breast cancer. Int J Cancer. 2018;142(7):1343\u0026ndash;54. \u003c/li\u003e\n\u003cli\u003eAmant F, Deckers S, Van Calsteren K, Loibl S, Halaska M, Brepoels L, et al. Breast cancer in pregnancy: Recommendations of an international consensus meeting. Eur J Cancer. 2010;46(18):3158\u0026ndash;68. \u003c/li\u003e\n\u003cli\u003eAmant F, Berveiller P, Boere IA, Cardonick E, Fruscio R, Fumagalli M, et al. Gynecologic cancers in pregnancy: Guidelines based on a third international consensus meeting. Ann Oncol. 2019;30(10):1601\u0026ndash;12. \u003c/li\u003e\n\u003cli\u003eCardonick E, Dougherty R, Grana G, Gilmandyar D, Ghaffar S, Usmani A. Breast cancer during pregnancy: Maternal and fetal outcomes. Cancer J. 2010;16(1):76\u0026ndash;82. \u003c/li\u003e\n\u003cli\u003eSilverstein J, Post AL, Chien AJ, Olin R, Tsai KK, Ngo Z, et al. Multidisciplinary Management of Cancer During Pregnancy. JCO Oncol Pract. 2020;16(9):545\u0026ndash;57. \u003c/li\u003e\n\u003cli\u003eLyons TR, Schedin PJ, Borges VF. Pregnancy and breast cancer: When they collide. J Mammary Gland Biol Neoplasia. 2009;14(2):87\u0026ndash;98. \u003c/li\u003e\n\u003cli\u003eHartman EK, Eslick GD. The prognosis of women diagnosed with breast cancer before, during and after pregnancy: a meta-analysis. Breast Cancer Res Treat. 2016;160(2):347\u0026ndash;60. \u003c/li\u003e\n\u003cli\u003eAmant F, Nekljudova V, Maggen C, Seither F, Neven P, Cardonick EH, et al. Outcome of breast cancer patients treated with chemotherapy during pregnancy compared with non-pregnant controls. Eur J Cancer. 2022;170(April):54\u0026ndash;63. \u003c/li\u003e\n\u003cli\u003eAmant F, Lefr\u0026egrave;re H, Borges VF, Cardonick E, Lambertini M, Loibl S, et al. The definition of pregnancy-associated breast cancer is outdated and should no longer be used. Lancet Oncol. 2021;22(6):753\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eRuiz R, Herrero C, Strasser-Weippl K, Touya D, St. Louis J, Bukowski A, et al. Epidemiology and pathophysiology of pregnancy-associated breast cancer: A review. Breast [Internet]. 2017;35(2017):136\u0026ndash;41. Available from: http://dx.doi.org/10.1016/j.breast.2017.07.008\u003c/li\u003e\n\u003cli\u003ede Haan J, Verheecke M, Van Calsteren K, Van Calster B, Shmakov RG, Mhallem Gziri M, et al. Oncological management and obstetric and neonatal outcomes for women diagnosed with cancer during pregnancy: a 20-year international cohort study of 1170 patients. Lancet Oncol. 2018;19(3):337\u0026ndash;46. \u003c/li\u003e\n\u003cli\u003eViuff JH, Greiber IK, Karlsen MA, Storgaard L, Kroman N, Jensen MB, et al. Survival in Women Diagnosed With Breast Cancer During Pregnancy. Clin Breast Cancer [Internet]. 2021;1\u0026ndash;9. Available from: https://doi.org/10.1016/j.clbc.2021.11.009\u003c/li\u003e\n\u003cli\u003eAmant F, Von Minckwitz G, Han SN, Bontenbal M, Ring AE, Giermek J, et al. Prognosis of women with primary breast cancer diagnosed during pregnancy: Results from an international collaborative study. J Clin Oncol. 2013;31(20):2532\u0026ndash;9. \u003c/li\u003e\n\u003cli\u003eAzim HA, Santoro L, Russell-Edu W, Pentheroudakis G, Pavlidis N, Peccatori FA. Prognosis of pregnancy-associated breast cancer: A meta-analysis of 30 studies. Cancer Treat Rev [Internet]. 2012;38(7):834\u0026ndash;42. Available from: http://dx.doi.org/10.1016/j.ctrv.2012.06.004\u003c/li\u003e\n\u003cli\u003eChuang SC, Lin CH, Lu YS, Hsiung CA. Association of pregnancy and mortality in women diagnosed with breast cancer: A Nationwide Population Based Study in Taiwan. Int J Cancer. 2018;143(10):2416\u0026ndash;24. \u003c/li\u003e\n\u003cli\u003eAlsaker MDK, Opdahl S, Romundstad PR, Vatten LJ. Association of time since last birth, age at first birth and parity with breast cancer survival among parous women: A register-based study from Norway. Int J Cancer. 2013;132(1):174\u0026ndash;81. \u003c/li\u003e\n\u003cli\u003eGiuliano AE, Connolly JL, Edge SB, Mittendorf EA, Rugo HS, Solin LJ, et al. Breast Cancer-Major changes in the American Joint Committee on Cancer eighth edition cancer staging manual. CA Cancer J Clin. 2017;67(4):290\u0026ndash;303. \u003c/li\u003e\n\u003cli\u003eCardonick E, Bhat A, Gilmandyar D, Somer R. Maternal and fetal outcomes of taxane chemotherapy in breast and ovarian cancer during pregnancy: Case series and review of the literature. Ann Oncol. 2012;23(12):3016\u0026ndash;23. \u003c/li\u003e\n\u003cli\u003eSchuurman TN, Witteveen PO, van der Wall E, Passier JLM, Huitema ADR, Amant F, et al. Tamoxifen and pregnancy: an absolute contraindication? Breast Cancer Res Treat [Internet]. 2019;175(1):17\u0026ndash;25. Available from: http://dx.doi.org/10.1007/s10549-019-05154-7\u003c/li\u003e\n\u003cli\u003eAndrikopoulou A, Apostolidou K, Chatzinikolaou S, Bletsa G, Zografos E, Dimopoulos MA, et al. Trastuzumab administration during pregnancy: un update. BMC Cancer. 2021;21(1):1\u0026ndash;12. \u003c/li\u003e\n\u003cli\u003eAmant F, Van Calsteren K, Halaska MJ, Gziri MM, Hui W, Lagae L, et al. Long-term cognitive and cardiac outcomes after prenatal exposure to chemotherapy in children aged 18 months or older: An observational study. Lancet Oncol [Internet]. 2012;13(3):256\u0026ndash;64. Available from: http://dx.doi.org/10.1016/S1470-2045(11)70363-1\u003c/li\u003e\n\u003cli\u003eCardonick EH, Gringlas MB, Hunter K, Greenspan J. Development of children born to mothers with cancer during pregnancy: Comparing in utero chemotherapy-exposed children with nonexposed controls. Am J Obstet Gynecol [Internet]. 2015;212(5):658.e1-658.e8. Available from: http://dx.doi.org/10.1016/j.ajog.2014.11.032\u003c/li\u003e\n\u003cli\u003eVandenbroucke T, Verheecke M, van Gerwen M, Van Calsteren K, Halaska MJ, Fumagalli M, et al. Child development at 6 years after maternal cancer diagnosis and treatment during pregnancy. Eur J Cancer. 2020;138:57\u0026ndash;67. \u003c/li\u003e\n\u003cli\u003eLejarraga HA. Pediatric outcome after maternal cancer diagnosed during pregnancy. Arch Argent Pediatr. 2016;114(2):e121\u0026ndash;2. \u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"reproductive-biology-and-endocrinology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"rbej","sideBox":"Learn more about [Reproductive Biology and Endocrinology](http://rbej.biomedcentral.com)","snPcode":"12958","submissionUrl":"https://submission.nature.com/new-submission/12958/3","title":"Reproductive Biology and Endocrinology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Breast cancer, pregnancy, chemotherapy, neonatal outcome","lastPublishedDoi":"10.21203/rs.3.rs-3901208/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3901208/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003ePregnancy-associated breast cancer (PABC) is a rare entity whose prognosis has previously been studied and is subject to controversy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eSurvival of patients with PABC diagnosed between 2009 and 2021 with breast cancer during pregnancy or until 1 year after childbirth was compared with non-pregnant patients with breast cancer from the same period at La Paz University Hospital. Cox proportional hazards regression was used to compare disease-free (DFS) and overall (OS) survival between the groups, adjusting for grade and pathologic stage.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong the 89 included patients with breast cancer, 34 were diagnosed during pregnancy, and 55 were not pregnant. The pregnant patients were more likely to have grade 3 tumors (61.3% vs 37%, p\u0026thinsp;=\u0026thinsp;0.023) and an advanced stage (pathologic stage III-IV: 44.1% vs 17.6%, p\u0026thinsp;=\u0026thinsp;0.008). Median follow-up was 47 months for the pregnant group and 46 months for the control group. After adjustments for tumor grade and pathologic stage, OS was comparable between the groups (HR 2.03; 95% CI 0.61 to 6.79; P\u0026thinsp;=\u0026thinsp;0.25).\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThe outcome of women diagnosed with PABC is comparable to young non-pregnant controls. However, it should be taken into account that PABC has a more aggressive phenotype.\u003c/p\u003e","manuscriptTitle":"Survival in Breast Cancer Patients Compared to Non-Pregnant Controls","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-01 16:04:16","doi":"10.21203/rs.3.rs-3901208/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-02-13T01:43:59+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-02-10T20:53:22+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"fb8ed563-beae-4191-bbf0-3d4761f3220e","date":"2024-02-03T19:37:51+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-02-02T02:43:24+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-01-31T01:57:36+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-01-31T01:57:36+00:00","index":"","fulltext":""},{"type":"submitted","content":"Reproductive Biology and Endocrinology","date":"2024-01-26T22:26:52+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"reproductive-biology-and-endocrinology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"rbej","sideBox":"Learn more about [Reproductive Biology and Endocrinology](http://rbej.biomedcentral.com)","snPcode":"12958","submissionUrl":"https://submission.nature.com/new-submission/12958/3","title":"Reproductive Biology and Endocrinology","twitterHandle":"@BioMedCentral","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"BMC/SO AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6f20978c-1e1b-40de-9e39-c7c9a3261f91","owner":[],"postedDate":"February 1st, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-04-01T15:11:12+00:00","versionOfRecord":{"articleIdentity":"rs-3901208","link":"https://doi.org/10.1186/s12958-024-01206-w","journal":{"identity":"reproductive-biology-and-endocrinology","isVorOnly":false,"title":"Reproductive Biology and Endocrinology"},"publishedOn":"2024-03-26 15:01:45","publishedOnDateReadable":"March 26th, 2024"},"versionCreatedAt":"2024-02-01 16:04:16","video":"","vorDoi":"10.1186/s12958-024-01206-w","vorDoiUrl":"https://doi.org/10.1186/s12958-024-01206-w","workflowStages":[]},"version":"v1","identity":"rs-3901208","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3901208","identity":"rs-3901208","version":["v1"]},"buildId":"GqpaHPwrfC8PjnIFayRh5","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}