Rosenberg, S

Abstract Background Young women are more likely than older women to present with higher stage breast cancer (BC) and may benefit to a greater extent from downstaging with neoadjuvant systemic treatment (NST). Young age is also associated with greater likelihood of pathologic complete response (pCR). Using a large prospective cohort of young women with BC, we investigated response to neoadjuvant therapy, eligibility for breast conserving surgery (BCS) pre- and post-NST, and surgical treatment. Methods The Young Women's Breast Cancer Study (YWS) is a multi-center cohort of women diagnosed with BC at age ≤40, that enrolled 1302 patients from 2006 to 2016. Disease characteristics and treatment information were obtained through medical record and central pathology review. Surgical recommendation before and after NST, conversion from BCS borderline/ineligible to BCS eligible, surgery, documented reasons for choosing mastectomy (MTX) among BCS eligible women, and final pathologic response were independently reviewed. Results Among 1302 women enrolled in YWS, 801 (62%) presented with unilateral stage I-III breast cancer and 317(40%) received NST. Median age was 36 years old (22-40). Pre-NST, 85/317 (27%) were BCS eligible, 49 (15%) were borderline, and 169 (53%) were not eligible (16 inflammatory breast cancer (IBC), 88 large tumor size /cosmetic, 48 diffuse calcifications, and 83 multicentricity). Among the 218 patients who were BCS ineligible/borderline pre-NST, 82 (38%) became eligible for BCS after NST. 4 patients who were BCS eligible pre-NST became ineligible. Of all patients eligible for BCS post-NST (n=163), 80 (49%) attempted BCS, 74 (93%) of whom were successful, and 83 (51%) chose MTX. Reasons for choosing MTX included: patient preference (38/83 (46%)), BRCA or TP53 mutation (31 (37%)), family history (3 (4%)), unknown (11 (13%)). On final pathology, 75 (24%) patients had pCR. Among patients who achieved a pCR, 48 (64%) underwent MTX, fewer than half (21/48 (44%)) were for anatomic indications (IBC, large tumor at diagnosis, diffuse calcifications, multicentric disease). Conclusion While NST doubled the proportion of young women eligible for BCS, nearly half chose MTX regardless of response to NST, mostly for personal preference or high-risk preventative reasons. These data highlight that surgical decision making among young women with breast cancer is often driven by factors beyond extent of disease and clinical response to therapy. Table 1.Clinical-pathologic characteristicsCharacteristicsNumber%Pre NST surgical recommendation BCS eligible8526.8Borderline4915.5BCS ineligible16953.3Unknown144.4Clinical Response Complete20263.7Partial9229.0Stable30.9Progressing72.2Unknown134.1Pathologic Response pCR (No invasive or DCIS)7524No pCR24276Post NST Surgical recommendation BCS eligible16351.4BCS ineligible14445.4Unknown103.2Attempted surgery BCS8025.2MTX23674.1Unknown20.6Final Surgery BCS7423.3MTX24176unknown20.6 Citation Format: Kim HJ, Dominici L, Rosenberg S, Pak LM, Poorvu PD, Ruddy K, Tamimi R, Schapira L, Come S, Peppercorn J, Borges V, Warner E, Vardeh H, Collins L, King T, Partridge A. Surgical treatment after neoadjuvant systemic therapy in young women with breast cancer: Results from a prospective cohort study [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-01.

Abstract Background: Chemotherapy can damage the ovaries and cause amenorrhea, a surrogate for infertility. Young women often wish to understand and minimize their risk of chemotherapy-related amenorrhea (CRA). However, the incidence of CRA with regimens that do not include either an anthracycline or cyclophosphamide is poorly studied. For patients with HER-2 positive disease, these anthracycline and cyclophosphamide-sparing regimens (e.g., docetaxel-carboplatin) are common (in combination with Her-2 directed therapy) in both the neoadjuvant and adjuvant settings. Methods: Women diagnosed with breast cancer under age 50 and within the past 10 years were recruited through a Dr. Susan Love Research Foundation Army of Women e-mail blast. Those who provided their contact information were mailed a consent form and medical record authorization form. Participants then received a web-based survey that inquired about receipt of and type of chemotherapy (including date of last dose) and date of last menstrual period (LMP). Patient-reported LMP was compared to date of final chemotherapy dose to determine if the LMP occurred before (defined as “CRA”) or after the last chemotherapy dose. When available, medical record data was used in place of survey data regarding type of chemotherapy used. Exclusion criteria included: LMP prior to diagnosis date, receipt of multiple chemotherapy regimens or no chemotherapy regimens, receipt of ovarian suppression medications (which interfere with interpretation of menstrual data), surgical menopause prior to or at the same time as diagnosis, a cancer diagnosis more than 10 years prior, incomplete menstrual data on the survey, report of an unknown chemotherapy regimen, and no date available for the last chemotherapy dose without an LMP within a month prior to survey completion. Fisher Exact test was used to compare CRA rates between regimens. Rates after two anthracycline-sparing regimens (taxane/cyclophosphamide; taxane/carboplatin) were compared to rates after anthracycline/cyclophosphamide/taxane. Results: 273 women consented to participate in this study, 258 of whom filled out the web survey. 151 of them were eligible for this analysis with a median age at diagnosis of 41 (range 24-49) and a median time from last chemotherapy dose to survey of 62.5 months (range 2-138). CRA occurred in 51.2% of the 86 participants who received an anthracycline, cyclophosphamide, and a taxane, in 41.9% of the 43 participants who received only a taxane and cyclophosphamide (p=0.35), and in 13.3% of the 15 participants who received carboplatin with a taxane (p=0.01). When the 11 patients who were <12 months since last chemotherapy were excluded, CRA rates changed minimally. Age did not differ by regimen, but median time since chemotherapy was shorter in the taxane/carboplatin group (35 months vs. 68 months). Trastuzumab with or without pertuzumab was administered in 100% of patients who received carboplatin/taxane, in 23.3% of patients who received taxane and cyclophosphamide, and in 22.1% of patients who received anthracycline/cyclophosphamide/taxane. Conclusions: This study suggests that carboplatin/taxane may be substantially less gonadotoxic than cyclophosphamide-based (neo)adjuvant regimens. Further research is necessary to confirm these findings. Citation Format: Gast KC, Cathcart-Rake EJ, Norman A, Eshragi L, Obidegwu N, Yost K, Nichols HB, Rosenberg S, Su HI, Stewart E, Couch F, Vachon C, Ruddy KJ. Regimen-specific rates of chemotherapy-related amenorrhea in breast cancer survivors [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-12-10.