A Unique Surgical Case of Mixed Metaplastic Breast Carcinoma With Heterologous Mesenchymal Differentiation and Conventional Adenocarcinomatous Elements.

Metaplastic breast carcinoma (MBC) is very rare among all invasive breast carcinomas, accounting for less than 1.0% of them. MBCs are classified into five subtypes, including mixed MBC - where the mix might be multiple metaplastic elements or a mixture of epithelial and mesenchymal elements. Overall survival for mixed MBC tends to correlate with a significantly worse outcome. Therefore, an early accurate diagnosis and surgical treatment for mixed MBCs must allow for an improved quality of life and better prognosis. However, there have not been many recently published papers describing the detailed cytological features of mixed MBCs on fine-needle aspiration (FNA) specimens. A 60-year-old female presented with a history of a hard breast mass on the left lateral side, showing an ill-defined and marginally enhanced tumor nodule on magnetic resonance imaging. The cytologic specimens of FNA contained a large number of three-dimensional, cohesive and sheet-like clusters, or non-cohesive single cells, of highly atypical spindled sarcomatoid to oval epithelioid cells having hyperchromatic pleomorphic nuclei and mitotic figures, in a necrotic and hemorrhagic background. A small amount of osteoid matrix-like substance was rarely seen, associated with a very small number of osteoclast-like giant cells. We first interpreted it as an invasive breast carcinoma of high grade. A mastectomy was performed, and a gross examination of the neoplasm revealed a hemorrhagic solid tumor lesion with a gray-whitish cut surface, measuring approximately 35 × 24 × 21 mm in diameter. On a microscopic examination, the tumor was predominantly composed of the proliferation of highly atypical oval to spindled cells predominantly in a sarcomatous growth fashion with focal production of chondroid and osteoid matrix, peripherally coexisted with a smaller volume of conventional invasive breast carcinoma. Immunohistochemistry showed that the sarcomatous tumor cells were specifically positive for vimentin, α-smooth muscle actin, or epithelial membrane antigen. Therefore, we finally made a diagnosis of invasive mixed MBC with heterologous mesenchymal differentiation and conventional adenocarcinomatous elements. To the best of our knowledge, this would most recently be the first case report of mixed MBC with heterologous mesenchymal differentiation and conventional adenocarcinomatous elements, with a focus on its FNA cytomorphologic findings. We should be aware that owing to its characteristic cytological features, cytopathologists might be able to make a correct diagnosis of MBC, based on multiple and adequate samplings.

Oncoplastic breast surgery to prevent "Bird's beak" deformity in the breast: a comparative retrospective study.

PURPOSES: Breast deformity occurring in the lower pole after breast conserving surgery (BCS) is known as bird's beak (BB) deformity. This retrospective study evaluated the outcomes in breasts reconstructed with a conventional closing procedure (CCP) and a downward-moving procedure (DMP), respectively, after BCS. METHODS: In CCP, the inferomedial and inferolateral portions of breast tissues were reapproximated toward the midline after wide excision to repair the breast defect. In DMP, the retro-areolar breast tissue was detached from the nipple-areolar complex after wide excision, and the upper pole breast tissue was moved downward to refill the breast defect. RESULTS: CCP was performed in 20 patients (Group A), and DMP was performed in 28 patients (Group B). Although retraction of the lower part of the breast was postoperatively observed in 13 (72%) of 18 patients from Group A, it was observed in 7 (28%) of 25 patients in Group B (p < 0.05). The downward pointing of the nipple was observed in 8 (44%) of 18 patients from Group A and in 4 (16%) of 25 patients in Group B (p < 0.05). CONCLUSIONS: DMP is more useful for preventing BB deformity than CCP.

Axillary Reverse Mapping in Clinically Node-Positive Breast Cancer Patients.

BACKGROUND: Axillary reverse mapping (ARM) nodes are involved in a significant proportion of clinically node-positive (cN+) breast cancer patients. However, neoadjuvant chemotherapy (NAC) is effective at decreasing the incidence of nodal metastases in cN+ patients. PATIENTS AND METHODS: One hundred forty-five cN+ patients with confirmed nodal involvement on ultrasound-guided fine needle aspiration cytology were enrolled in this study: one group underwent axillary lymph node dissection (ALND) without NAC (upfront surgery group), and the other group underwent ALND following NAC (NAC group). The patients underwent 18F-FDG-positron emission tomography/computed tomography (18F-FDG-PET/CT) before surgery, as well as an ARM procedure during ALND. RESULTS: the rates of involvement of ARM nodes in the NAC group were significantly lower than those of the upfront surgery group (36.6% vs. 62.2%, p < 0.01). Notably, involvement was significantly decreased after NAC in non-luminal-type tumors as compared to the luminal-type (18.4% vs. 48.5%: p < 0.01). Moreover, there was a significant difference in ARM node involvement after NAC between patients with or without axillary uptake of 18F-FDG (61.5% vs. 32.5%: p < 0.01). CONCLUSIONS: NAC significantly decreased the risk of ARM node metastases in cN+ patients, but 18F-FDG-PET/CT was not suitable to detect residual metastatic disease of the axilla after NAC.

FXYD3 functionally demarcates an ancestral breast cancer stem cell subpopulation with features of drug-tolerant persisters.

The heterogeneity of cancer stem cells (CSCs) within tumors presents a challenge in therapeutic targeting. To decipher the cellular plasticity that fuels phenotypic heterogeneity, we undertook single-cell transcriptomics analysis in triple-negative breast cancer (TNBC) to identify subpopulations in CSCs. We found a subpopulation of CSCs with ancestral features that is marked by FXYD domain-containing ion transport regulator 3 (FXYD3), a component of the Na+/K+ pump. Accordingly, FXYD3+ CSCs evolve and proliferate, while displaying traits of alveolar progenitors that are normally induced during pregnancy. Clinically, FXYD3+ CSCs were persistent during neoadjuvant chemotherapy, hence linking them to drug-tolerant persisters (DTPs) and identifying them as crucial therapeutic targets. Importantly, FXYD3+ CSCs were sensitive to senolytic Na+/K+ pump inhibitors, such as cardiac glycosides. Together, our data indicate that FXYD3+ CSCs with ancestral features are drivers of plasticity and chemoresistance in TNBC. Targeting the Na+/K+ pump could be an effective strategy to eliminate CSCs with ancestral and DTP features that could improve TNBC prognosis.

Conservative Axillary Surgery May Prevent Arm Lymphedema without Increasing Axillary Recurrence in the Surgical Management of Breast Cancer.

Axillary lymph node dissection (ALND) has been associated with postoperative morbidities, including arm lymphedema, shoulder dysfunction, and paresthesia. Sentinel lymph node (SLN) biopsy emerged as a method to assess axillary nodal status and possibly obviate the need for ALND in patients with clinically node-negative (cN0) breast cancer. The majority of breast cancer patients are eligible for SLN biopsy only, so ALND can be avoided. However, there are subsets of patients in whom ALND cannot be eliminated. ALND is still needed in patients with three or more positive SLNs or those with gross extranodal or matted nodal disease. Moreover, ALND has conventionally been performed to establish local control in clinically node-positive (cN+) patients with a heavy axillary tumor burden. The sole method to avoid ALND is through neoadjuvant chemotherapy (NAC). Recently, various forms of conservative axillary surgery have been developed in order to minimize arm lymphedema without increasing axillary recurrence. In the era of effective multimodality therapy, conventional ALND may not be necessary in either cN0 or cN+ patients. Further studies with a longer follow-up period are needed to determine the safety of conservative axillary surgery.

The involvement of axillary reverse mapping nodes in patients with node-positive breast cancer.

INTRODUCTION: Axillary reverse mapping (ARM) procedure is useful in reducing lymphedema. However, concerns regarding oncologic safety have limited the adoption of the ARM procedure. This study aimed to evaluate the involvement of ARM nodes in node-positive breast cancer patients. MATERIALS AND METHODS: Two hundred twenty-three node-positive patients were enrolled in this study: 90 were clinically node-negative, but had one or more positive sentinel lymph nodes (SLNs) (SLN-positive group); 68 were clinicopathologically node-positive (CpN-positive group); and 65 had confirmed nodal involvement and received neoadjuvant chemotherapy (NAC) (NAC group). All patients underwent axillary lymph node dissection with fluorescent ARM. RESULTS: ARM nodes were involved in 33 (36.7%) patients of the SLN-group. Residual ARM nodes after SLN biopsy were involved in 11 patients (12.2%), including 5 patients (19.2%) with crossover type nodes and 6 patients (9.4%) with non-crossover type nodes. However, the difference in involvement rates between the two types was not high enough to be significant. Of these 11 patients, moreover, four patients had three or more than 3 involved SLNs. On the other hand, the involvement rate of ARM nodes in the NAC group was significantly lower than that of the CpN-positive group (35.4% vs. 64.7%: p < 0.01). Despite lower involvement, the risk of metastases in the ARM nodes was still too high to spare ARM nodes in both the NAC group and CpN-positive group. CONCLUSIONS: Suspicious or involved ARM nodes should be removed even when detected in ARM procedure, particularly in NAC-group and CpN-positive-group patients.

Conservative axillary surgery is emerging in the surgical management of breast cancer.

Axillary lymph node dissection (ALND) has been the standard axillary treatment for breast cancer for a long time. However, ALND is associated with postoperative morbidities, including local sensory dysfunction, reduced shoulder mobility and most notably arm lymphedema. Recently, ALND can be avoided not only in clinically node-negative (cN0) patients with negative sentinel lymph nodes (SLNs), but also in patients with less than 3 positive SLNs receiving breast radiation, axillary radiation, or a combination of the two. Moreover, SLN biopsy has been adopted for use in clinically node-positive (cN +) patients presenting as cN0 after neoadjuvant chemotherapy (NAC); ALND may be avoided in cN + patients who convert to SLN-negative following NAC. Patients who undergo SLN biopsy alone have less postsurgical morbidities than those who undergo ALND. Nevertheless, ALND is still required in a select group of patients. A variety of conservative approaches to ALND have been developed to spare arm lymphatics to minimize arm lymphedema. These conservative procedures seem to decrease the incidence of lymphedema without increasing axillary recurrence. In the era of effective multimodality therapy, full conventional ALND removing all microscopic axillary disease may now be unnecessary in both cN0 patients and cN + patients. Regardless, emerging procedures for ALND should still be considered as investigational approaches, as further studies with longer follow-up are necessary to determine the safety of conservative ALND to spare arm lymphatics.

Recurrent malignant phyllodes tumor of the breast: An extremely rare case of recurrence with only rhabdomyosarcoma components.

Rhabdomyosarcoma is a rare disease that typically occurs in children. Rhabdomyosarcoma seldom occurs in the breast, and its diagnosis and treatment have infrequently been reported. The present case is a rare one of a recurrent malignant phyllodes tumor of the breast with only rhabdomyosarcoma components. A 69-year-old woman received a diagnosis of borderline phyllodes tumor of the left breast and underwent partial mastectomy. During follow-up, a left breast mass was found 1 year and 8 months after the previous surgery. Based on examination findings, it was suspected to be recurrent phyllodes tumor, so total left mastectomy was performed in our hospital. After the surgery, immunostaining failed to determine the epithelial component which may be produced by the proliferative part of stromal cells of previous phyllodes tumors. However, we could not exclude the possibility that this was a new tumor. After comparing samples with specimens from the first operation, it was finally determined to be a malignant phyllodes tumor with a rhabdomyosarcoma component. Therefore, chemotherapy was given, and vincristine, actinomycin D, and cyclophosphamide therapy was introduced. At the same time, radiation therapy was planned. Among phyllodes tumors, cases involving rhabdomyosarcoma components are very rare, especially those where the recurrence morphology only shows the same rhabdomyosarcoma components. This was a rare case with unique characteristics and great reference value.

Case-based survey: The impact of breast-cancer treatment on fertility in Japan.

AIM: To assess the impact of breast-cancer treatment on fertility. METHODS: We conducted a retrospective, case-based survey of treatments administered for infertility and pregnancy outcomes after patients underwent treatment for breast cancer. Surveys were distributed to breast oncology facilities and reproductive endocrinology and infertility (REI) facilities. RESULTS: As high as 60% of the pregnancies in women under the age of 35 years occurred spontaneously. Additionally, the fertility rates decreased as age increased (under 35 years of age: 40%, 35-39 years of age: 21%, 40-44 years of age: 10%, respectively). In women who became pregnant after treatment for breast cancer, conception was achieved within 1 to 3 years after beginning to try for pregnancy. CONCLUSIONS: After treatment for breast cancer, women can expect spontaneous pregnancy, especially if they are under 35 years of age. It is important for patients 35 years of age and older to commence assisted reproductive technology in a timely manner when pursuing fertility after treatment for breast cancer.

The role of axillary reverse mapping in intraoperative nodal palpation during sentinel lymph node biopsy.

Intraoperative nodal palpation in the axilla is a mandatory part of sentinel lymph node biopsy. However, there is no consensus regarding the definition of suspicious palpable node. The sampling rate and involvement rate of suspicious palpable nodes are inconsistent. We hypothesized that axillary reverse mapping is helpful to select suspicious palpable sentinel lymph nodes more accurately. Patients with clinically negative nodes underwent sentinel lymph node biopsy with intraoperative nodal palpation and axillary reverse mapping. Blue and hot nodes were removed as sentinel lymph nodes. Suspicious palpable nodes that were neither blue nor hot were removed as palpable sentinel lymph nodes. Nodes around blue and hot sentinel lymph node were incidentally removed as para-sentinel lymph nodes. Fluorescent nodes were considered axillary reverse mapping nodes. Patients with positive sentinel lymph node underwent axillary lymph node dissection. Palpable sentinel lymph nodes and para-sentinel lymph nodes were removed in 130 (15%) of 850 patients with clinically negative nodes. Although palpable sentinel lymph nodes and para-sentinel lymph nodes were involved in 19 (15%) of 130 patients, fluorescent palpable sentinel lymph nodes were involved only in 2 patients and fluorescent para-sentinel lymph nodes were not involved. When excluding fluorescent palpable sentinel lymph nodes and para-sentinel lymph nodes, the sampling rate of suspicious palpable nodes significantly decreased (15% vs. 5%, p < 0.01) and the involvement rate of palpable sentinel lymph nodes significantly increased (15% vs. 31%, p < 0.05). Axillary reverse mapping is helpful to avoid an unnecessary removal of palpable nodes without metastases.

Meta-analysis of nanoparticle albumin-bound paclitaxel used as neoadjuvant chemotherapy for operable breast cancer based on individual patient data (JBCRG-S01 study).

BACKGROUND: Nanoparticle albumin-bound paclitaxel (nab-PTX), a novel taxane formulation, was developed to avoid cremophor/ethanol-associated toxicities including peripheral neuropathy and hypersensitivity. At least 35 phase II studies using combined nab-PTX and anthracycline in neoadjuvant settings are registered in Japan. We analyzed the efficacy and safety of nab-PTX based on patient characteristics in these studies. METHODS: We conducted a meta-analysis using individual patient data (IPD) to investigate the average efficacy of nab-PTX-containing regimens as neoadjuvant chemotherapy for operable breast cancer. IPD were provided by principal investigators who agreed to participate. The primary endpoint was pathological complete response (pCR) rate of each breast cancer subtype. RESULTS: We analyzed the data of 16 studies involving 753 patients. The overall crude frequencies of pCR (ypT0 ypN0, ypT0/is ypN0, and ypT0/is ypNX) were 18.1, 26.0, and 28.6%, respectively. Specifically, the frequencies were 6.7, 10.2, and 13.4% for luminal (n = 343); 40.5, 63.5, and 68.9% for human epidermal growth factor receptor 2 (HER2)-rich, (n = 74); 21.9, 40.6, and 42.7% for luminal/HER2 (n = 96); and 26.3, 31.5, and 32.3% for triple-negative breast cancers (TNBC) (n = 232). The multivariate analyses indicated that HER2 positivity, TNBC, high Ki-67, high nuclear grade, and weekly nab-PTX administration were significantly associated with the pCR. The proportion of hematological toxicities (neutropenia (39.7%) and leukopenia (22.5%)), peripheral sensory neuropathy (9.7%), myalgia (5.7%), and arthralgia (4.7%) was higher than grade 3 adverse events, but most patients recovered. CONCLUSIONS: Nab-PTX is a safe and acceptable chemotherapeutic agent in neoadjuvant settings, particularly for aggressive cancers. UMIN-CTR#: UMIN000028774.

Neural EGFL like 2 expressed in myoepithelial cells and suppressed breast cancer cell migration.

Breast tissue has a branching structure that contains double-layered cells, consisting primarily of luminal epithelial cells inside and myoepithelial cells outside. Ductal carcinoma in situ (DCIS) still has myoepithelial cells surrounding the cancer cells. However, myoepithelial cells disappear in invasive ductal carcinoma. In this study, we detected expression of neural EGFL like (NELL) 2 and one of its receptors, roundabout guidance receptor (ROBO) 3, in myoepithelial and luminal epithelial cells (respectively) in normal breast tissue. NELL2 also was expressed in myoepithelial cells surrounding the non-cancerous intraductal proliferative lesions and DCIS. However, the expression level and proportion of NELL2-positive cells in DCIS were lower than those in normal and non-cancerous intraductal proliferative lesions. ROBO3 expression was decreased in invasive ductal carcinoma compared to that in normal and non-cancerous intraductal proliferative lesions. An evaluation of NELL2's function in breast cancer cell lines demonstrated that full-length NELL2 suppressed cell adhesion and migration in vitro. In contrast, the N-terminal domain of NELL2 increased cell adhesion in the early phase and migration in vitro in some breast cancer cells. These results suggested that full-length NELL2 protein, when expressed in myoepithelial cells, might serve as an inhibitor of breast cancer cell migration.

Axillary surgery for breast cancer: past, present, and future.

In breast cancer surgery, there has been a major shift toward less invasive local treatment. Although axillary lymph node dissection (ALND) was an integral part of surgical treatment for breast cancer, sentinel lymph node (SLN) biopsy was developed as an accurate method for axillary staging. ALND can be avoided not only in patients with negative SLNs but also in those with one or two positive SLNs receiving breast and/or axillary radiation. On the other hand, ALND has remained the standard treatment for patients with clinically positive nodes. However, axillary reverse mapping (ARM) was developed to map and preserve arm lymphatic drainage during ALND and/or SLN biopsy. This procedure allowed reduction of the rate of arm lymphedema without increasing axillary recurrence, although patients receive postoperative chemotherapy and high-risk patients undergo axillary radiation. Standard ALND may not be necessary even for patients with clinically positive nodes who receive axillary radiation and systemic therapy. Thus, the extent of axillary surgery in breast cancer has been decreased with increased use of systemic and radiation therapy.

A case of recurrent malignant phyllodes tumor undergoing nipple-sparing mastectomy with immediate breast reconstruction.

BACKGROUND: Although the primary treatment for malignant phyllodes tumor (PT) is complete surgical excision with either breast-conserving surgery or total mastectomy, recent technical advances have led to the adoption of nipple-sparing mastectomy (NSM) with immediate breast reconstruction (IBR). CASE PRESENTATION: A 28-year-old woman noticed a mass in her left breast that was rapidly increasing in size. She underwent tumor excision and a histological diagnosis of marked degenerative and necrotic induration suggested benign PT. One year later, however, she was found to have recurrent masses in the left breast on follow-up mammography and sonography. Needle biopsy was performed and the tumor was diagnosed as borderline or malignant PT. She underwent NSM and sentinel lymph-node biopsy with IBR using a tissue expander. Histological examination of the mastectomy specimen showed multiple fibroepithelial tumors with marked stromal overgrowth, focal necrosis, and hemorrhage. Stromal cells showed pleomorphism and a maximal mitotic rate of approximately 25 per 10 high-power fields. The tumor was diagnosed as malignant PT. She did not receive adjuvant chemotherapy or radiation treatment. At 3-year follow-up, the patient remains free of disease and highly satisfied with the cosmetic results. CONCLUSIONS: NSM with IBR is not a contraindication for malignant PT. It is both curative and can offer an appealing cosmetic option for localized malignant PT.

Nationwide survey of Japanese breast oncology and reproductive endocrinology departments about the impact of breast cancer treatment on fertility.

The purpose of this study is to assess the impact of breast cancer treatment on the reproductive potential. We conducted a nationwide survey of breast oncology and reproductive endocrinology and infertility (REI) departments using a questionnaire designed to assess the impact of breast cancer treatment on fertility. We received responses from 312 breast oncology departments (response rate, 31.9%) and 541 REI departments (response rate, 50.9%). The most common method of achieving pregnancy reported by breast oncology departments was natural insemination (69.6%), followed by assisted reproductive technology ( 15.6%) and intrauterine insemination (IUI; 14.8%). The most common method of achieving pregnancy reported by REI departments was conventional in vitro fertilization and/or intracytoplasmic sperm injection (51.0%), followed by natural insemination with or without ovulation induction (40.0%) and IUI (8.0%). The overall pregnancy rate for patients who underwent treatment for infertility at REI departments after breast cancer treatment was 39.0%. Vast patients who experienced breast cancer treatments conceived mainly by natural insemination based on the data from breast oncology departments. On the other hand, 61.0% of the patients who visited REI departments presumably due to infertility by natural insemination did not conceive even by infertility treatments with exclusive knowledge in REI departments.

Axillary reverse mapping in patients undergoing axillary dissection -a short review of the literature.

Axillary lymph node dissection (ALND) can be avoided not only in patients with negative sentinel lymph nodes (SLNs) but also in those with one or two positive SLNs receiving breast or axillary radiation. However, ALND has remained the standard treatment for patients with clinically positive nodes (cN+). Although axillary reverse mapping (ARM) was developed to map and preserve arm lymphatic drainage during ALND, it could not be indicated for cN + patients because metastatic rate of ARM nodes is high. However, a new type of conservative ALND with ARM attempts to preserve ARM lymphatics and nodes except SLNs and other suspicious palpable nodes, including suspicious ARM nodes. This procedure allowed reduction of the rate of arm lymphedema without increasing axillary recurrence, although patients received postoperative chemotherapy and high-risk patients underwent axillary radiation. Thus, a traditional full ALND may not be necessary for cN + patients in the era of effective multimodality therapy.

A unique surgical case of giant invasive intracystic carcinoma of the male breast focusing on cytological findings.

A 60-year-old male presented with a history of a relatively hard and cystic right chest mass that had gradually increased in size, with subsequent skin erosion, exudate and hemorrhage. The cytologic specimens from a cyst fluid contained a large number of sheet-like or papillary clusters of atypical cuboidal to columnar epithelial cells with loss of myoepithelial components, in a severely inflammatory background with scattered siderophages. We first interpreted it as a carcinoma, but could not completely exclude out the possibilities of benign. Tumor extirpation was performed, and a gross examination of the neoplasm revealed a giant, cystic and partly solid papillary-projected tumor lesion, with a gray-whitish cut surface, associated focally with skin invasion, measuring approximately 9 × 7 cm with a 6 × 4 cm solid area in diameter. On a microscopic examination, solid parts of the tumor were predominantly composed of the intracystic proliferation of mildly atypical epithelial cells with absence of two-cell patterns in a papillary or papillotubular growth fashion, only partly involving the dermis to epidermis. Immunohistochemistry showed that the carcinoma cells were specifically positive for estrogen and progesterone receptors, whereas negative for p63, S-100 protein and several neuroendocrine markers. Therefore, we finally made a diagnosis of invasive intracystic carcinoma of the male breast. We should be aware that owing to its characteristic cytological features, cytopathologists might be able to make a correct diagnosis of that, based on multiple and adequate samplings, even though a core biopsy would be the absolute minimum assessment.

The relation between anti-TGBFR1 immunohistochemical reaction and low Ki67, small tumor size and high estrogen receptor expression in invasive breast cancer.

Most breast cancers are derived from the luminal epithelium, which composes the inside of the breast ductal structure. Ductal carcinoma in situ (DCIS) leads to invasive ductal carcinoma, but noncancerous intraductal proliferative lesions are also a risk factor for ductal carcinoma. The transforming growth factor beta (TGFB) signaling pathway behaves as a tumor suppressor in the early stage of cancer, and conversely as a tumor growth factor in invasive stages in several cancers. In this study, we performed immunohistochemistry with an antibody that detects the cytoplasmic region of TGFB receptor 1 (TGFBR1) and elucidated TGFBR1 protein expression in luminal epithelial cells of noncancerous breast ducts and in several cases of DCIS and invasive carcinoma. TGFBR1 expression was higher in noncancerous breast tissue than in cancerous tissue, and a difference in expression was also seen among histological subtypes. Comparing the expression level of TGFBR1 in cancer cells and clinico-pathological parameters, cases expressing low TGFBR1 tended to show low estrogen receptor expression, large tumor size (≥10 mm), and a high Ki67 labeling index. These data suggested that TGFBR1 protein expression may be related to the suppression of breast cancer cell growth.

Ovarian hyperstimulation closely associated with resumption of follicular growth after chemotherapy during tamoxifen treatment in premenopausal women with breast cancer: a multicenter retrospective cohort study.

BACKGROUND: We previously reported that tamoxifen (TAM)-induced ovarian hyperstimulation (OHS) is associated with high serum concentrations of estradiol in premenopausal women with breast cancer. To investigate risk factors for TAM-induced OHS, we performed a retrospective multicenter study. METHODS: Premenopausal patients who received surgical therapy for endocrine-dependent breast cancer (n = 235) were recruited in this study and classified into 4 groups: group A, treated with TAM alone; group B, TAM treatment after 2-year-combined therapy with a gonadotropin-releasing hormone (Gn-RH) agonist; group C, TAM treatment after chemotherapy; group D, 5-year-combined therapy with TAM and a Gn-RH agonist. A serum estradiol value of more than 300 pg/mL or mean follicular diameter of more than 30 mm was defined as OHS. RESULTS: The incidence of OHS in group A (n = 13/26, 50.0%) was significantly higher than those in group B (n = 17/63, 27.0%), group C (n = 20/110, 18.2%), and group D (n = 0/36, 0%). The incidence of OHS was significantly correlated with aging, and the median serum concentration of estradiol in the presence of OHS was 823.0 pg/mL. The incidence of OHS (less than 47 years old) was 62.5% in group A, 48.6% in group B, and 28.2% in group C, respectively. Notably, the incidence rate of OHS following amenorrhea in group C (n = 13/20, 65.0%) was significantly higher than that in group B (n = 1/17, 5.9%). CONCLUSIONS: These findings indicate that the onset of OHS following amenorrhea was common in the post-chemotherapeutic group, while its ratio was low in the group after Gn-RH analog treatment, suggesting that combined treatment-based management involving TAM therapy is necessary for premenopausal patients with breast cancer.