Bridging across the pacific: overview of the 33rd annual meeting of the Japanese breast cancer society.

Ovarian suppression for adjuvant treatment of hormone receptor-positive early breast cancer.

Background. Breast cancer (BC) is the leading cause of cancer-related death in young women worldwide, and late recurrence of hormone receptor-positive disease plays a substantial role. Adjuvant endocrine therapy with 5 years of ovarian function suppression (OFS) and an aromatase inhibitor or tamoxifen is recommended for many young patients with high risk hormone receptor-positive BC. Data are limited regarding extended endocrine therapy among premenopausal BC survivors, and non-existent to inform treatment decisions regarding extending OFS beyond 5 years. We sought to evaluate young BC survivors’ perceptions and preferences regarding extending OFS beyond 5 years, and consideration of a potential future study to assess the role of extended OFS. Methods. From January-April 2023, email invites were sent to the Young Survival Coalition (YSC) listserv (N=14,291) specifically asking members with a history of invasive BC (≤45 years at diagnosis; stage I-III without metastatic recurrence) receiving OFS injections for adjuvant endocrine treatment to complete a one-time anonymous online survey. The survey was designed to capture information regarding current endocrine therapy use, patient-provider communication regarding extended endocrine therapy including OFS, OFS-related concerns (rating 0-5 [low: 0-1, moderate: 2-3, severe: 4-5]), and interest in a potential future clinical trial utilizing OFS beyond 5 years. Descriptive statistics were utilized to summarize responses, and two-sided Fishers exact tests and chi-square analyses were used for comparisons. Results. A total of 1,030 YSC members completed the survey, and 615 were analyzed due to eligibility and completeness of data. The majority were from the United States (n=579, 94.1%) or Canada (n=8, 1.3%), were non-Hispanic white (n=452, 73.5%), non-Hispanic Black (n=46, 7.5%), or Hispanic (n=43, 7.0%), and had been diagnosed with stage II BC (n=316, 51.4%). The average age at survey was 38.1 years (SD=5.15, range=22-54) and at initial BC diagnosis was 34.6 years (SD=4.96, range=20-49). Most (n=510, 83.0%) were within their first 5 years of OFS treatment while 14.5% (n=89) had already been receiving OFS for more than 5 years. Many respondents (n=344, 55.9%) reported discussing OFS use beyond 5 years with their provider, of whom 39.8% (n=245) reported their provider recommending they continue OFS for more than 5 years. Despite reporting moderate and severe concerns regarding OFS side effects (n=476, 77.4%), inconvenience of injection visits (n=272, 44.2%), and high cost of medication (n=223, 36.3%), most respondents (n=396, 64.4%) would consider continuing OFS beyond 5 years if it would reduce risk of BC recurrence. For nearly half of respondents (n=289, 47.0%) a risk reduction of at least 5% would be required for extended OFS to be worthwhile compared to the remaining 46.3% (n=285) who indicated interest for < 5% risk reduction. When asked hypothetically if they would take part in a clinical trial to determine efficacy of OFS use beyond 5 years, the majority were interested (n=357, 58.0%). Respondents who were interested were less likely to be concerned about the high cost of medication (p=0.003) however they were also less likely to take OFS beyond 5 years if it only led to 1-2% BC risk reduction (p=0.006) compared to those who were not interested. There were no other proportional differences on any other outcome. Conclusion. Many BC survivors and providers are already considering incorporation of OFS beyond 5 years into adjuvant endocrine therapy despite harboring concerns and lack of data. Efforts to determine the efficacy and benefits of extended OFS are necessary given the risk of late recurrence in this population as well as the potential for significant short- and long-term toxicities. The results from this survey study suggest that future clinical trials evaluating potential benefits and risks of long-term OFS use among young BC survivors are needed and likely feasible. Citation Format: Kate Dibble, Tal Sella, Kathryn Ruddy, Craig Snow, Amanda Nixon, Patricia Spears, Karla Ballman, Lisa Carey, Ann Partridge. Ovarian function suppression (OFS) use beyond five years?: Young breast cancer patient preferences [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-01-11.

Implementation science and breast cancer control: A Breast Health Global Initiative (BHGI) perspective from the 2010 Global Summit

Background Recent publication of Suppression of Ovarian Function (SOFT) and Tamoxifen and Exemestane (TEXT) trials provides additional options for premenopausal women with hormone receptor (HR)-positive breast cancer in improving estrogen blockade - tamoxifen (T) plus ovarian function suppression (OFS) and aromatase inhibitors (AI) plus OFS. Analysis of these trials conclude that, for a premenopausal woman with HR-positive breast cancer with high risk features for recurrence have an absolute benefit for five-year breast cancer free interval (BCFI) would be 5% with the use of T + OFS and 10 - 15% with AI + OFS compared to the usof T-alone. However, therapeutic option decision-making is dependent on the oncologists' perception of the benefit and risk for adjuvant anti-estrogen therapy. We aimed to evaluate an oncologist's perception of the absolute benefit for anti-estrogen therapy options in HR–positive breast cancer and identify predictors for variations in perceptions of benefit. Methods We designed a survey using a clinical vignette of a young, premenopausal woman with stage IIIA HR-positive breast cancer with high risk of recurrence. After obtaining Institutional Review Board (IRB) approval from the University of Kentucky, we sent online and paper survey forms to a convenience sample of 510 oncologists in the United States. Using a scale between 0 and 100, the oncologists were asked to estimate the five-year BCFI (first occurrence of invasive locoregional, distant or contralateral breast cancer) for a woman with similar characteristics if treated with the following: 1) lumpectomy (L) + Radiation (RT); 2) L + RT + chemotherapy (C); 3) L + RT + C + T x five years; 4) L + RT + C + T + OFS; and 5) L + RT + C + AI + OFS. Baseline demographics such as gender, practice setting (academic vs community), years in practice and proportion of breast cancer patients in practice were also collected. Results The highest estimated mean five-year BCFI for the study patient was 76.5% with the addition of AI + OFS to L + RT + C. The estimated absolute benefit for anti-estrogen therapy options: T + OFS vs T-alone was 3.4% (95% CI: 2.7 – 4.0) and for AI + OFS vs T-alone was 5.9% (95% CI: 5.1 – 6.7). Oncologists' Perception of Absolute Benefit Therapy in Premenopausal Women with Breast CancerAnti-Estrogen Therapy5-year BCFI (mean)Standard DeviationL+ RT43.6+/- 18.6L + RT + C59.5+/- 15.5L + RT + C + T x 5 year70.6+/- 13.4L + RT + C + T + OFS74.1+/- 12.9L + RT + C + AI + OFS76.5+/- 12.7 There was no difference in perception of benefit with these anti-estrogen therapy options by gender, practice setting, years in practice or proportion of breast cancer patients seen in practice. Discussion Regardless of their gender, practice setting, clinical experience or volume of breast cancer patients, oncologists significantly underestimate the absolute benefit for various estrogen blockade therapies when compared to the estimated benefit of data from randomized, controlled SOFT and TEXT clinical trial data. We highlight an area for improvement in quality of care that offers an immediate impact on positive outcomes for large numbers of premenopausal women with breast cancer. Citation Format: Patel RA, Maxwell S, Yan D, Dressler E, Mathew A. Oncologists' perception of anti-estrogen therapy benefit [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-15-05.

The quest to define optimal endocrine therapy for premenopausal women with early-stage breast cancer began more than 50 years ago but is still unfulfilled. Multiple strategies have emerged, including tamoxifen, ovarian function suppression (OFS) by surgery, luteinizing hormone–releasing hormone agonist or radiation, and combination strategies such as tamoxifen plus OFS or aromatase inhibitor plus OFS. An added confounder is that these strategies have frequently been assessed in the context of adjuvant chemotherapy, which is commonly used in premenopausal women and may have indirect endocrine effects because of chemotherapy-induced menopause. This complex landscape was reviewed in a 2011 American Society of Clinical Oncology (ASCO) endorsement of the 2010 Cancer Care Ontario guideline recommending against the routine use of OFS in addition to tamoxifen or chemotherapy and a 2014 ASCO guideline endorsing consideration of 10 years of tamoxifen for these young women with hormone-responsive disease. Against this backdrop, in the article that accompanies this editorial, Tevaarwerk et al report the final results of a phase III Eastern Cooperative Oncology Group trial (E-3193, INT-0142) in which 345 premenopausal women with lymph node–negative, hormone receptor–positive breast cancer measuring 3 cm were randomly assigned from 1994-1997 to receive 5 years of tamoxifen alone or 5 years of tamoxifen plus OFS; no chemotherapy was permitted. With a median follow-up of almost 10 years, there were no significant differences in the primary end points of disease-free survival (DFS; 87.9% v 89.7% P .62) or overall survival (95.2% v 97.6%; P .67). Secondary end points included toxicity and several patient-reported outcomes (PROs) including menopausal symptoms, sexual function, and health-related quality of life. These results suggest that tamoxifen plus OFS leads to increased toxicity, more menopausal symptoms, and reduced sexual function, peaking around year 3 and then diminishing over time. The strengths of this study include the importance of the question, the clean design that enabled the testing of hormone therapies in the absence of chemotherapy, the focus on hormone-responsive tumors, the balance between the arms, the long follow-up, and the assessment of PROs. The major limitation is, of course, that the study’s early closure as a result of poor accrual left it vastly underpowered for its primary end points; this trial fell victim to the 1997 report of National Surgical Adjuvant Breast and Bowel Project (NSABP) B20, which recommended the use of chemotherapy in addition to tamoxifen for women with axillary lymph node–negative, hormoneresponsive breast cancer, especially women younger than 50 years of age. However, E-3193 was a success in its collection of detailed PROs, and it is noteworthy that it met the prespecified target accrual for these secondary end points. Given the exceptional outcomes for patients enrolled onto this trial, which had greater than 95% overall survival in the absence of chemotherapy, such patient-reported data are valuable contributions to the discussion between physicians and patients about the risks and benefits of individual therapies. Several crucial questions remain. Given the statistical limitations of this trial, might the combination of OFS plus tamoxifen actually be better than tamoxifen? What about the combination of OFS plus an aromatase inhibitor, given the efficacy of aromatase inhibitors in postmenopausal hormone receptor–positive breast cancer? Three large trials are helping to address these two questions: ABCSG-12 (Austrian Breast and Colorectal Cancer Study Group trial 12), SOFT (Suppression of Ovarian Function Trial), and TEXT (Tamoxifen and Exemestane Trial). A lingering concern is how we can integrate the results of all of these trials that use 3 to 5 years of adjuvant endocrine therapy with the findings of the ATLAS (Adjuvant Tamoxifen: Longer Against Shorter) and aTTom (Adjuvant Tamoxifen—To Offer More?) trials, which support the use of 10 years of tamoxifen. In the SOFT trial, 3,066 premenopausal women with hormoneresponsive breast cancer were randomly assigned to 5 years of tamoxifen, tamoxifen plus OFS, or exemestane plus OFS; (neo)adjuvant chemotherapy was permitted as long as patients remained premenopausal at its completion. In the TEXT trial, 2,672 premenopausal patients with hormone-responsive breast cancer were randomly assigned to receive 5 years of tamoxifen plus OFS or exemestane plus OFS; endocrine therapy was started concurrently with chemotherapy if chemotherapy was planned. Because of lower than expected event rates, the statistical plans for these two trials were revised some years ago to enable a joint analysis of 4,690 women receiving tamoxifen plus OFS versus exemestane plus OFS. In contrast to E-3193, 42% of these women were lymph node positive, and 57% received some type of chemotherapy. At a median follow-up of 68 months, a significantly improved DFS was seen with exemestane plus OFS (91.1% v 87.3%; HR, 0.72; 95% CI, JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 32 NUMBER 35 DECEMBER 1

Achieving advance care planning in diverse, underserved populations

Coming changes to mammography standards: With its proposed amendments to update mammography rules, the US Food and Drug Administration hopes to empower patients and health care providers.

Breast cancer is the most commonly diagnosed invasive cancer among women both globally and within the United States and the number one cause of cancer-related deaths among women globally ([1, 2][1]). Less than 1% of diagnosed breast cancers occur in men ([2][2]) and, therefore, male breast cancer is

What effect does mammographic breast density have on lesion detection in digital mammography?

Facilitating consensus by examining patterns of treatment effects

Background: The introduction of multigene assays has significantly altered the indications for adjuvant chemotherapy in hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2-) early breast cancer. The 70-gene signature (MammaPrintTM) test has demonstrated its ability to identify prognostic capability. Patients with high clinical risk classified as low risk by MammaPrintTM (MP) can be safely spared adjuvant chemotherapy. However, it is worth noting that the majority of clinical studies conducted on MP have predominantly involved Caucasian populations. Breast cancer is known to exhibit biological and clinical differences across different ethnicities and races. In China, the onset of breast cancer occurs a decade earlier than in Western populations, with an average age of diagnosis at 48.7 years and a peak incidence between 45 to 49 years. The prevalence of breast cancer among patients under 50 is significantly higher than in Western countries. Consequently, it is crucial to validate the performance of MP across diverse populations to ensure its generalizability and reliability. This study aimed to explore the real-world utilization of MP among Chinese patients. Method: From March 2018 to June 2022, genomic analysis utilizing the 70-gene platform, MammaPrintTM, was conducted on a consecutive series of 637 patients. An evaluation was performed to assess the distribution of clinicopathological characteristics across various risk groups as determined by the MP assay. This assessment was further compared with the findings from the pivotal MINDACT trial to indentify any notable differences. A robust analysis was conducted using the Kaplan-Meier method for survival curves and the Cox proportional hazards model to estimate hazard ratios. Results: Among the 637 patients enrolled in the study, 261 (41.0%) were identified as high risk, with a substantial majority, 214 (82.0%), undergoing chemotherapy. In contrast, 376 (59.0%) were categorized as low risk, with a significantly smaller proportion, 46 (12.2%), receiving chemotherapy. A stark contrast was observed in the distribution of risk categories between the two groups, with a statistical significance (p < 0.001). Patients characterized by tumor grade 1, Ki67<30%, and PR ≥ 20% were predominantly classified as low risk. Compared to the MINDACT study population, the patients in this cohort were notably younger, with 33.3% versus 56.2% being under 50 years of age, and had larger tumors with higher tumor grades (p < 0.001). Notably, younger patients, those with Ki67≥ 30%, and lymph node-positive patients were more inclined to receive chemotherapy, even when classified as low risk. Conversely, older patients in the high-risk group were less likely to be treated with chemotherapy. During a median follow-up period of 33 months (8 -66 months), 17 events were recorded. No significant difference in breast cancer free interval (BCFI) was observed between genetically high and low-risk groups for all patients (96.5% vs 97.3%, P=0.28), including those under 50 years of age (95.5% vs 97.5%, P=0.863). However, among patients aged 50 or older, those classified as genetically low risk exhibited a superior BCFI compared to their high-risk counterparts (98.9% vs. 97.1%, P=0.047). It was interesting to observe that the BCFI significantly improved following ovarian function suppression in patients under 50 years of age identified as low risk, compared to those without such suppression (P=0.035). Nonetheless, no significant difference was noted between the two groups for high-risk patients (P=0.115). Conclusion: The real-world data clearly illustrate the benefits of the MP assay in decreasing the necessity for adjuvant chemotherapy in Chinese patients with low genomic risk in HR+/HER2- early breast cancer. The recurrence rates were similar in the high and low risk groups, which might be due to the favorable prognosis of the study population, the effectiveness of tailored treatments in managing breast cancer across different risk profiles and the short follow-up period. The poorer prognosis observed in high-risk patients aged 50 or older might be attributed to the fact that a significant number older patients did not receive chemotherapy. Our data showed that low-risk patients under the age of 50 could benefit from ovarian function suppression. This finding warrants further investigation. Citation Format: Weijuan Jia, Yongwen Jiang, Anqin Zhang, Fengxia Gan, Qian Ouyang. Early-stage HR+/HER2- breast cancer patients under 50 years old with a low-risk identified by the 70-gene signature (MammaPrintTM) could benefit from ovarian function suppression: A real-world study in China [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2024; 2024 Dec 10-13; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2025;31(12 Suppl):Abstract nr P1-11-12.

Introduction: Mammographic density (MD) has been reported to be associated with increased risk of breast cancer development. In addition, the association of MD with breast cancer subtypes has been proposed in Caucasian breast cancer patients but this has remained virtually unknown in Asian patients. Therefore, in this study, we retrospectively examined the subtypes and clinical prognosis in Japanese cancer patients according to their MD. Method: We retrospectively examined 781 mammograms of breast cancer patients from March 2013 to March 2016 at Nahanishi Clinic, Okinawa, Japan. In this study, MD was tentatively classified according to the recommendation of the Japanese Central Organization on Quality Assurance of Breast Cancer Screening, based on the proportion of fat area as follows; (a) extremely high dense:10-20%, (b) heterogeneously dense:40-50%, (c) scattered fatty:70-90%, (d) fatty: almost all the breast fat. “Dense breast” includes extremely high and heterogeneous dense. We also evaluated the rates of recurrence and breast cancer specific death according to MD defined as above. The status of breast cancer subtypes was also compared between dense and non-dense breasts, and between pre-menopausal and post-menopausal women. Result: Among 781 cases examined, 365 were classified as dense breasts and 416 as non-dense breasts. The median age of all the patients examined was 57 years old. The age was significantly younger (50.4 vs 63.4 years old P<0.001), and the BMI significantly lower (22.2 vs 25.9 P<0.001) in the dense breast group. No significant differences of the breast cancer mass diameter were detected between dense and non-dense breasts (23mm vs 20.8mm P=0.10). At 49.7 months median observation period, the rate of breast cancer death (HR: 0.98(0.43-2.21), P=0.96) nor the recurrence rate (HR:1.64(0.95-2.84), P=0.078) were not different between dense and non-dense breasts. The rate of hormone receptor positive breast cancer was significantly higher in non-dense breasts (OR 0.66(0.44-0.98) P=0.049) but HER2 positivity was significantly higher in dense breasts (OR 1.66(1.11-2.49) P=0.017). The triple negative subtype was significantly higher in non-dense breasts (OR 0.49(0.27-0.929) P=0.032). Ki67 labeling index was higher in dense breast patients (24.3% vs 20.3%,P=0.004). There were no significant differences in the rate of hormone positive tumors between dense and non-dense breasts in patients under 40 years of age (OR 1.14(0.27-4.79), P=0.85) but its rate was significantly lower in patients over 60 years of age with dense breasts (OR 0.51(0.26-0.98), P=0.043). In addition, in a separate analysis of all women who regularly received mammogram examination at our clinic during the same period, among 2308 subjects under the age of 40, 1892 subjects had dense breasts and 417 subjects had non-dense breasts, in which the incidence of hormone positive breast cancer was not significantly different between these two groups (OR 0.92(0.47-1.79), P=0.94). However, among the 4340 subjects over 60 years of age, the incidence of hormone positive breast cancers in the 1158 dense group was significantly smaller than the 3182 non-dense group (OR 0.73(0.55-0.97), P=0.033). Conclusion: Results of our present study firstly demonstrated that the rate of breast cancer death and recurrence was not significantly different between patients with dense and non-dense breasts. However, our results specifically taken from Asian women indicated that the rate of hormone positive tumors was significantly higher in non-dense breasts, especially in post-menopausal women, contrary to existing reports which suggested that was higher in dense breast in Caucasian women. Citation Format: Naoko Takigami, Kentaro Tamaki, Yoshihiko Kamada, Kano Uehara, Seiko Tsuchiya, Shigeharu Terukina, Takanori Ishida, Minoru Miyashita, Keely May McNamara, Hironobu Sasano, Nobumitsu Tamaki. A study of clinical outcome and biomarker profiles of Japanese breast cancer patients according to mammographic density [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-01-01.

Background: Although tamoxifen (TAM) plus ovarian function suppression (OFS) is one of standard adjuvant treatments in premenopausal women with hormone receptor-positive breast cancer, the optimal duration of OFS has not been clearly established. Patients and Methods: We retrospectively reviewed data of premenopausal patients with breast cancer, who received TAM and OFS (goserelin or leuprorelin) as adjuvant therapy between February 2004 and April 2015. The primary analysis was to compare disease-free survival (DFS) between patients who received OFS shorter than 3 years and those who received OFS longer than 3 years. The analyses were performed with Cox proportional hazards models and propensity score matching models. Results: We analyzed 206 premenopausal patients with hormone receptor-positive breast cancer. Median follow-up time was 56 months. Median age was 42 years (range, 24-52 years). Twenty six per cent of the patients had positive axillary nodes and 30% had received neo-adjuvant or adjuvant chemotherapy. Median duration of OFS was 26 months. Duration of OFS was shorter than three years (OFS < 3y) in 74% patients, and longer than three years (OFS > 3y) in 26% patients. Patients with node-positive disease were more in OFS > 3y group than in OFS < 3y group, and more patients received chemotherapy in OFS > 3y group than in OFS < 3y group. 5-year disease-free survival (DFS) was 96.1%. DFS in patients aged ≤ 40 years and aged > 40 years were 91.8% and 99.0%, respectively (p=0.0223). Propensity score matching model showed that DFS was not significantly different between patients in OFS < 3y group and those in OFS > 3y group (97.4%, 91.6%; p=0.2406). In patients aged ≤ 40 years and/or those who received chemotherapy, 5-year DFS was 96.7% in OFS < 3y group, 90.1% in OFS > 3y group (p=0.3011). Conclusions: Our data suggest that OFS < 3y is not inferior to OFS > 3y for premenopausal women with hormone receptor-positive breast cancer as adjuvant endocrine therapy. A randomized trial is needed to establish the optimal OFS duration for these patients. Citation Format: Ozaki Y, Tamura N, Utiyama M, Masuda J, Koganemaru S, Miura Y, Tanabe Y, Ogura T, Kadowaki M, Miura D, Kawabata H, Takano T. Duration of ovarian function suppression for premenopausal women with hormone receptor-positive breast cancer: Retrospective study. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-12-11.

Background It is uncertain if the addition of OFS to adjuvant endocrine therapy with T improves outcomes in premenopausal HR+ BC. The SOFT trial was designed to determine the value of OFS in women who remain premenopausal and are treated with T (OFS question) and also to test whether an AI improves outcome in premenopausal women with HR+ BC treated with OFS (AI question). In the combined analysis of the TEXT and SOFT trials (AI question), the group treated with the AI exemestane+OFS had a significantly better disease-free survival (DFS) than those with T+OFS. This abstract presents the results of the OFS question (n=2,045). Patients and Methods Between November 2003 and January 2011, the SOFT phase 3 trial randomized 3066 premenopausal women with HR+ BC to 5 years of adjuvant endocrine therapy with exemestane+OFS versus T+OFS versus T alone, with OFS initiated by choice of GnRH agonist triptorelin, oophorectomy or ovarian irradiation. Prior chemotherapy was allowed, provided women had confirmed premenopausal estradiol levels within 8 months of completing chemotherapy. The primary end point was DFS which included invasive local, regional, distant and contralateral breast events, second non-breast malignancies and deaths without prior cancer. Because of a lower-than expected overall event rate and to ensure results within a reasonable time-frame, a protocol amendment in 2011 changed the originally event-driven analysis plan. The amendment (1) designated the comparison of T+OFS versus T alone as the primary analysis for SOFT (n=2045), recognizing that the statistical power for the original three pairwise comparisons would be substantially reduced and (2) specified that the primary analysis of T+OFS versus T be undertaken when median follow-up was at least 5 years. The comparison would be tested at the 2-sided 0.05 level with no interim analysis. Based on the projected number of events at the lower rates, the estimated power to detect hazard ratios of 0.75, 0.70, and 0.66 for the comparison would be 52%, 69%, and 80%. Results The SOFT trial completed planned patient enrollment with an international collaboration involving 426 centres from BIG and NABCG led by the International Breast Cancer Study Group (IBCSG). Numbers of patients randomized, randomization strata, and pt age are summarized in the Table. The database lock for the primary analysis of the OFS question will occur in September 2014 and the final analysis will be completed by October 15, 2014. SOFT Patients (%)Tamoxifen alone1021 (33%)Tamoxifen+OFS1024 (33%)Exemestane+OFS1021 (33%)* Prior Chemotherapy54%Lymph node positive35%Median age (% < 40 years)43 years (30%)*Patients randomized to Exemestane+OFS are not part of the current analysis Conclusions We will present the primary analysis of outcomes and toxicities by treatment for women randomized to receive T+OFS versus T and address the value of OFS in addition to T as adjuvant endocrine therapy for premenopausal women with HR+ BC. Citation Format: Aron Goldhirsch, Richard D Gelber, Prudence A Francis, Meredith M Regan, Gini F Fleming, Istvan Lang, Eva M Ciruelos, Meritxell Bellet, Herve Bonnefoi, Miguel A Climent, Lorenzo Pavesi, Harold J Burstein, Silvana Martino, Nancy E Davidson, Charles E Geyer Jr, Barbara A Walley, Robert E Coleman, Pierre Kerbrat, Manuela Rabaglio-Poretti, Alan S Coates. Randomized comparison of adjuvant tamoxifen (T) plus ovarian function suppression (OFS) versus tamoxifen in premenopausal women with hormone receptor-positive (HR+) early breast cancer (BC): Analysis of the SOFT trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr S3-08.

507 Background: In young women with hormone receptor-positive (HR+) breast cancer (BC), ovarian function suppression (OFS) has been shown to improve outcomes when combined with adjuvant endocrine therapy (ET). However, limited evidence exists on its efficacy in germline BRCA (gBRCA) carriers. Here we investigated the association between OFS plus ET and outcomes in the largest global cohort of young g BRCA carriers with BC. Methods: The BRCA BCY Collaboration (NCT03673306) is an international, multicenter, hospital-based, retrospective cohort study of women harboring germline BRCA1/2 pathogenic/likely pathogenic variants, diagnosed between 2000 and 2020 with stage I-III invasive BC at age of ≤ 40 years. The analysis included patients with HR+ BC and available data on ET and OFS. The OFS group included patients treated with luteinizing hormone-releasing hormone agonists (LHRHa) and/or bilateral risk-reducing salpingo-oophorectomy (RRSO) within 1 year of BC diagnosis. Outcome analyses included disease-free survival (DFS), BC-free interval (BCFI) and overall survival (OS). Cox proportional hazard models, stratified for country, year of diagnosis, nodal status, and surgery type and adjusted for RRSO and bilateral risk-reducing mastectomy (time-dependent), were used to explore the association between OFS use (vs non-use) and outcomes. Sensitivity analysis explored OFS as time-dependent covariate. To address immortal time bias, an additional Cox model accounted for left truncation, considering differences in time to BRCA testing. Results: Among 5,660 patients from 109 centers, 1,865 patients with HR+ BC were included, of whom 1,071 (57%) received OFS plus ET ( 35% with an aromatase inhibitor [AI], 65% with tamoxifen [tam])and 794 (43%) received tam alone. Patients receiving OFS were more likely to have node-positive disease (56% vs 47%), receive treatment in recent years (36% vs 17%), undergo mastectomy (70% vs 57%) and be tested for g BRCA at diagnosis (46% vs 30%). With a median follow-up of 7.8 years (IQR 4.6-12.1), OFS combined with ET was associated with significantly improved DFS (adjusted HR [aHR] 0.79, 95% CI 0.66-0.94), BCFI (aHR 0.74, 95% CI 0.61-0.89) and OS (aHR 0.66, 95% CI 0.50-0.88) over tam alone. Sensitivity analysis using OFS as a time-dependent factor yielded consistent results. No significant interactions were observed between OFS use and specific g BRCA mutations or HER2 status. Sub-analyses by type of ET (OFS + AI vs. OFS + tam vs. tam alone) will be presented at the conference. Conclusions: In this global cohort of young BRCA mutation carriers, OFS combined with ET was associated with improved DFS, BCFI and OS versus tam without OFS. These findings support the consideration of OFS as a key component of adjuvant therapy in this population.