Laparoscopic bilateral salpingo-oophorectomy for recurrent ovarian endometriotic cysts in a woman taking adjuvant tamoxifen for breast cancer: A case report

A 38-year-old Japanese woman (gravida 1, para 1) presented with severe, long-term menstrual pain. Transvaginal ultrasonography and contrast-enhanced magnetic resonance imaging showed a 3-cm multifocal mass in the right adnexa ( Fig. 1 , Fig. 2 ), which was clinically diagnosed as a right ovarian endometriotic cyst. On the basis of the tumor size, the decision was made to initiate conservative management with low-dose estrogen-progestin (LEP) rather than plan surgery. Transvaginal ultrasonography at 6 months showed a decreased diameter of the cyst. The cystic lesion continued to shrink, and transvaginal ultrasonography at regular visits revealed that the cystic lesion eventually almost disappeared. Fig. 1 Magnetic resonance T2-weighted image of an ovarian endometriotic cyst (arrow) in a 38-year-old woman. A horizontal T2-weighted image is shown. The ovarian endometriotic cyst is shown as heterogeneous low-signal intensity in the form of shading on T2-weighted imaging. Fig. 1 Fig. 2 Magnetic resonance T1-weighted image of an ovarian endometriotic cyst (arrow) in a 38-year-old woman. A horizontal T1-weighted image is shown. The ovarian endometriotic cyst is shown as hyperintensity on T1-weighted imaging. Fig. 2 Magnetic resonance T2-weighted image of an ovarian endometriotic cyst (arrow) in a 38-year-old woman. A horizontal T2-weighted image is shown. The ovarian endometriotic cyst is shown as heterogeneous low-signal intensity in the form of shading on T2-weighted imaging. Magnetic resonance T1-weighted image of an ovarian endometriotic cyst (arrow) in a 38-year-old woman. A horizontal T1-weighted image is shown. The ovarian endometriotic cyst is shown as hyperintensity on T1-weighted imaging. When the patient reached 45 years of age, owing to concerns about thrombosis because of her age, she was switched from LEP to dienogest (DNG). After initiating DNG, no recurrence of the endometriotic cyst was shown on transvaginal ultrasonography. When the patient was 46 years of age, ductal carcinoma was found during a biopsy at another hospital. Partial left mastectomy and a sentinel node biopsy were performed, and the diagnosis was left breast cancer (L-A, Bp, microinvasive carcinoma, pT1mi, Ly0, V0, g, estrogen receptor[+], progesterone receptor[+], p53[+], human epidermal growth factor receptor 2[−], and MIB-1 LI: 13.7%). Postoperatively, the patient was started on radiation therapy followed by TAM. Following a breast exam, DNG was ceased, and menstruation resumed thereafter. Four months postoperatively, a 3-cm cystic lesion on the right ovary was shown on transvaginal ultrasonography. During follow-up, a left ovarian mass was observed, which was suspected to be an endometriotic cyst, and the left ovarian cystic lesion had increased to 7 cm ( Fig. 3 ). Therefore, she was admitted for laparoscopic surgery. During this period, TAM was continued. Fig. 3 Transvaginal ultrasonographic image of an ovarian endometriotic cyst in the patient at 46 years of age. A 7-cm-sized low-echoic cystic lesion (arrow) on the left side of the uterus can be seen. Fig. 3 Transvaginal ultrasonographic image of an ovarian endometriotic cyst in the patient at 46 years of age. A 7-cm-sized low-echoic cystic lesion (arrow) on the left side of the uterus can be seen. Laparoscopic bilateral salpingo-oophorectomy was performed ( Fig. 4 ). The postoperative pathological diagnosis was an endometriotic cyst in both ovaries, with no malignant findings in the bilateral adnexa. After consultation with the breast surgery department of another hospital, switching from TAM to an aromatase inhibitor was considered because the patient had undergone bilateral adnexectomy. Fig. 4 Laparoscopic image. During the operation, we found a 7-cm-sized cystic lesion (arrow) in the left ovary. Fig. 4 Laparoscopic image. During the operation, we found a 7-cm-sized cystic lesion (arrow) in the left ovary.

Various recent changes in the social environment have greatly affected women's diseases. As women enter the workforce, their lifestyles markedly change, and while the birth rate is declining, the childbearing age continues to increase owing to later marriages [ 2 ]. The decline in the fertility rate, which has become a social issue in Japan, is remarkable. However, the decline in the birth rate for those in their 20s and the increase in the birth rate for those in their 30s and 40s are also notable. Consequently, in Japan, the average age of first childbirth exceeded 30 years in 2015, and more than half of all women who give birth now have their first child when they are older than 30 years. The trend toward fewer children and later marriages has resulted in a lower incidence of childbearing and lactation. This trend along with a younger age at menarche and older age at menopause have resulted in an average increase in the number of menstrual cycles over a woman's lifetime [ 2 ]. An increased risk of developing endometriosis-related disease through menstrual blood reflux into the abdominal cavity and a reduced opportunity for early atrophy of endometriotic lesions with pregnancy is caused by this increase in the number of menstrual cycles [ 2 ]. Furthermore, the lengthening of the time to first childbirth and the shortened period of avoidance of estrogen exposure through pregnancy, childbirth, and lactation result in longer estrogen exposure in Japanese women in their lifetime [ 2 ], contributing to an increased incidence of breast cancer [ 5 ]. The diversification of conservative and surgical treatments, including LEP and other hormonal agents, and laparoscopic surgery have enabled longer treatment for endometriosis [ 2 ]. In Japan, between 2000 and 2008, LEP and progestin drugs were successively covered by insurance, which enabled safe, long-term drug therapy for endometriosis. Simultaneously, advances in technology and equipment have made laparoscopic and other surgical treatments widely available, and the treatment of endometriosis is currently more long-term than previously. In a national survey of endometriosis treatment rates by age group [ 2 ] it was shown that the peak age was 30–34 years in 1997, but 40–44 years in 2014. It is therefore suggested that endometriosis treatment has become more common over the past 20 years at older ages and for longer periods of time. Prolonged endometriosis treatment has led to an increase in the number of patients who develop breast cancer during the treatment period. The use of TAM is based on strong evidence for preventing postoperative recurrence of breast cancer and has shown excellent efficacy in breast cancer treatment. However, the risk of developing endometrial polyps, endometrial cancer, uterine fibroids, uterine sarcomas, and endometriosis is increased by the use of TAM [ 4 ]. It was shown in the National Surgical Adjuvant Breast and Bowel Project, a placebo-controlled, randomized, controlled trial of endometrial polyps in the United States, that the relative risks of developing endometrial polyps while taking TAM were 1.9 (95% confidence interval, 1.55–2.41) and 2.4 (95% confidence interval, 1.76–3.24) in premenopausal and postmenopausal women, respectively. Similarly, increased risks were observed for uterine leiomyoma, endometriosis, and endometrial hyperplasia [ 6 ]. In a meta-analysis conducted by the Early Breast Cancer “Trialists” Collaborative Group, the risk of endometrial cancer was increased in women receiving TAM who were over 55 years of age, but the risk was not significantly increased in women aged under 55 years receiving TAM. The mechanism by which TAM increases the risk of endometrial disease remains unclear [ 7 ]. Theories that TAM is genotoxic and produces DNA adducts that cause mutations, and that TAM itself has estrogen-like effects are likely correct [ 8 ]. Regarding uterine cancer screening during TAM administration, no evidence of early endometrial cancer has been observed, and there are disadvantages of performing invasive tests. Therefore, regular uterine cancer screening is not recommended in several countries, including the United States [ 7 ]. However, in Japan, it is recommended by the Oncology Committee of the Japanese Society of Obstetrics and Gynecology that all patients receiving TAM should undergo gynecological examinations immediately after starting administration because it is a risk factor for uterine cancer [ 6 ]. In a study by Nishiyama et al., ovarian endometriotic cysts developed because of TAM administration even after hysterectomy [ 9 ]. Therefore, during TAM administration, sufficient attention should be paid to the development of endometrial disease. Endometrial cytology is not as widely used in the United States as in Japan, and patients in Japan tend to value the detection of abnormalities despite the cost [ 6 ]. Therefore, regular gynecological examinations during TAM administration are considered essential, at least in Japan. In this case, the patient developed breast cancer while undergoing treatment for endometriosis, and TAM administered to prevent recurrence of breast cancer exacerbated the endometriosis, which had been stable. Endometriosis is a common problem, particularly among women in their 30s and 40s who are busy with work and childrearing. Pharmacological therapies, such as LEP and DNG, and minimally invasive endoscopic surgery can allow an early return to normal life. Therefore, when selecting a treatment method, the patient's symptoms and lifestyle should be carefully considered. Additionally, as previously mentioned, gynecological follow-up is important during TAM administration, and appropriate breast cancer treatment should be selected in collaboration with breast surgery. Postoperative conversion from TAM to an aromatase inhibitor may be a useful option in patients who have had bilateral adnexal removal [ 10 , 11 ]. In conclusion, the incidence of endometriosis has recently been increasing, partly because of changes in the social environment, including the declining birth rate. Although the increased number of treatment options including hormone therapy has enabled long-term conservative treatment, the incidence of breast cancer during the course of endometriosis has also increased, and there are an increasing number of situations in which the choice of the treatment method must be carefully considered. Particular attention should be paid to the development of endometriosis during TAM treatment after the development of breast cancer. Furthermore, management of endometriosis requires flexible treatment options, such as surgical therapy, depending on the patient's stage of life and medical condition. Although medical care cannot provide a fundamental solution to the decline in birth rate, appropriate endometriosis treatment is important in maintaining women's fertility.

Endometriosis is affects approximately 10% of menstruating women [ 1 ]. The treatment is frequently long-term and affects women's quality of life. Moreover, in Japan, the overall fertility rate continues to decline, largely owing to women getting married later in life. This has been associated with an increase in the number of menstrual cycles that women experience over their lifetime, and uninterrupted menstruation has become a major factor in the development of endometriosis [ 2 ] while long-term estradiol exposure has also increased the incidence of breast cancer [ 3 ]. Tamoxifen (TAM), which is used to prevent the postoperative recurrence of breast cancer, has an endometrial proliferation effect. Therefore, patients receiving TAM for managing endometrial diseases require particular attention [ 4 ]. The patient in the present case developed breast cancer during conservative treatment of an ovarian endometriotic cyst and underwent laparoscopic bilateral salpingo-oophorectomy owing to cyst recurrence during TAM administration. The case and the relevant literature are discussed.