Partridge, Ann H.

TPS595 Background: Patients (pts) with HER2+ early breast cancer (EBC) and invasive residual disease (RD) after neoadjuvant therapy (NAT) have a higher risk of relapse than pts with a pathologic complete response (pCR). Post neoadjuvant T-DM1 has improved invasive disease-free survival (iDFS), but pts with estrogen receptor (ER)-negative or nodal RD have suboptimal outcomes and recurrences in the central nervous system are a problem. More effective treatment strategies are needed. The CompassHER2 trials, EA1181 and A011801, leverage pCR to tailor post neoadjuvant therapy in HER2+ EBC. EA1181 is a NAT de-escalation trial of a taxane, trastuzumab and pertuzumab (THP) in clinical stage II-III HER2+ EBC; pts with a pCR complete HP +/- adjuvant radiation (RT) +/- endocrine therapy (ET). A011801 is an escalation trial for pts with high risk HER2+ RD after NAT, examining addition of the HER2 selective tyrosine kinase inhibitor (TKI) tucatinib to adjuvant T-DM1. Methods: Eligibility and Intervention: Pts. with high-risk HER2+ RD (e.g. ER-,node-positive, or both) after a predefined course of neoadjuvant HER2-directed treatment are randomized 1:1 to adjuvant T-DM1+ placebo (pb), vs. T-DM1 and tucatinib with adjuvant RT +/- ET. Eligibility criteria include completion of ≥ 6 cycles of NAT, including ≥ 9 weeks of T and H +/- P. All chemotherapy (CT) must be completed preoperatively unless participating in EA1181 (̃15-30% enrollees); these pts must receive postoperative CT to complete ≥ 6 cycles prior to enrollment on A011801. Pts who received prior HER2-targeted TKIs or antibody-drug conjugates are ineligible. Objectives: The primary objective is to determine if iDFS is higher with addition of T-DM1 to tucatinib in pts with HER2+ EBC with RD after NAT; secondary endpoints include overall survival, breast cancer free survival, distant recurrence-free survival, brain metastases-free survival and disease-free survival. Correlative objectives include the association of i) tumor infiltrating lymphocyte (TILs) levels in the primary tumor and RD with iDFS, ii) TILs with tucatinib benefit, iii) iDFS and circulating tumor cells (CTC) at serial timepoints and iv) the magnitude of benefit of tucatinib (iDFS) in pts with/without detectable pretreatment CTCs. Quality of life and pharmacokinetic endpoints will also be evaluated. Statistics: A011801 is a prospective, double-blind, randomized, phase III superiority trial; stratified by i) receipt of postoperative CT (Y/N), ii) hormone receptor-status (+/-),and iii) pathologic lymph node status (+/-). The study targets an absolute difference of 5% in iDFS (control vs. experimental arm 82% & 87%, HR = 0.7), with a two-sided alpha of 0.05 and power of 80%. The sample size is 981; target accrual = 1031 pts; activation and completion dates are 01/6/21 and ̃ 01/2028. Support: U10CA180821, U10CA180882; Seagen Inc; ClinicalTrials.gov Identifier: NCT04457596 Clinical trial information: NCT04457596.

BackgroundThe diagnosis and treatment of breast cancer can have profound effects on a young woman's family planning and fertility, particularly among women with hormone receptor–positive breast cancer.MethodsThe Young Women's Breast Cancer Study was a multicenter cohort of women aged 40 years or younger and newly diagnosed with breast cancer from 2006 to 2016. Surveys included assessments of fertility concerns, endocrine therapy (ET) preferences, and use. Characteristics were compared between women who reported that fertility concerns affected ET decisions and those who did not. Logistic regression was used to identify factors associated with having an ET decision affected by fertility concerns.ResultsOf 643 eligible women with hormone receptor–positive, stage I to III breast cancer, one‐third (213 of 643) indicated that fertility concerns affected ET decisions. In a multivariable analysis, only parity at diagnosis was significantly associated with fertility concerns affecting ET decisions (odds ratio for nulliparous vs ≥2 children, 6.96; 95% confidence interval, 4.09‐11.83; odds ratio for 1 vs ≥2 children, 5.30; 95% confidence interval, 3.03‐9.87). Noninitiation/nonpersistence was higher among women with fertility concerns versus those without fertility concerns (40% vs 20%; P < .0001). Among women with fertility‐related ET concerns, 7% (15 of 213) did not initiate ET, and 33% (70 of 213) were nonpersistent over 5 years of follow‐up. Of these women, 66% (56 of 85) reported 1 or more pregnancies or pregnancy attempts; 27% (15 of 56) had resumed ET at the last available follow‐up through 5 years.ConclusionsConcern about fertility is a contributor to adjuvant ET decisions among a substantial proportion of young breast cancer survivors. Ensuring family planning is addressed in the setting of ET recommendations should be a priority throughout the cancer care continuum.

Abstract BackgroundCancer diagnosis and early treatment may have wide-ranging consequences for a woman’spartner (ie. spouse or significant other). In general, younger caregivers have been found to havegreater unmet needs and higher levels of distress compared to those who are older. To date,there is little known about the unmet needs and experiences of partners who care for youngwomen with breast cancer during active treatment.Trial Design: Cross-sectional survey of partners of young women with breast cancer.Eligibility Criteria: The current analysis focuses on a subset of respondent partners of womenwith breast cancer participating in the Young Womens Breast Cancer Study (NCT01468246)who met the following criteria: diagnosed at age &lt; 40 years; time since diagnosis &lt;12 months;and/or Stage IV disease (at diagnosis or in metastatic setting); and/or local recurrent disease&lt; 12 months.Specific Aims: To explore the experience of partners of women in active treatment or havingvery recently completed treatment for breast cancer.Statistical Methods: We employed descriptive statistics to present sample characteristics,including means or medians for continuous variables and proportions for categorical variables.We assessed partners’ responses re: sociodemographics, perceived social support (MOS-Social Support Survey, Cancer Perceived Agents of Social Support), quality of life (QOL)(Caregiver QOL Index-Cancer), coping (Brief COPE), perceived financial security, perceivedparenting concerns (Parenting Concerns Questionnaire), anxiety and depression symptoms(Hospital Anxiety and Depression Scale), sexual satisfaction (Global Measure of SexualSatisfaction), posttraumatic growth (Posttraumatic Growth Inventory-Short Form), and an open-ended question to explore their experiences and needs.Accrual: 25 participants were included.Results: All partners were male (25/25; 100%), and most were white (n=23/25; 92%), workingfull-time (n=21/25; 91%); and college educated (n=19/25; 86%). Eighteen partners (n=18/25;72%) were parenting children &lt;18 years old and 40% (n=10/25) were partnered with womenwith Stage 4 breast cancer. At the time of the survey, the median age of partners was 44 years(range, 28-69) and of patients was 38 years (range, 25-40). Many partners (57%) reportedsymptoms of anxiety (&gt;8 on the HADS anxiety subscale), fewer (22%) were categorized ashaving symptoms of depression (&gt;8 on the HADS depression subscale). Additionally, 39%reported not being sexually active; 41% reported maladaptive coping; 30% reported financialstrain;30% reported relationship strain. Reported caregiver QOL ranged from 22-116, with amean score of 52.5 (SD, 23.9), similar to population norms, with higher scores indicating lowerquality of life. Parenting concerns scores were generally low indicating less concern, with arange of 12-35, and mean of 20.5 (SD, 7.6). Post-traumatic growth ranged from 4-33, with amean score of 20.7 (SD, 7.4), with higher scores indicating greater personal growthexperienced. 44% (11/25) responded to the open-ended experiences and needs question.Common responses included feeling a lack of support, need for tailored and titrated information,and desire to connect with other men who faced similar experiences. Partners also reportedtheir struggles with uncertainty about the future. Discussion: A subset of partners of young women in active treatment for breast cancerexpressed concerns related to relationship strain, sexuality, need for support, and finances.Future work designed to meet the needs of partners of breast cancer patients includinginformational and psychosocial supports may benefit them and the patients as they manage theprocess of ongoing treatment and challenges about the future. Citation Format: Tamryn F Gray, Nancy Borstelmann, Shoshana Rosenberg, Shari Gelber, Meghan E Meyer, Kathryn J. Ruddy, Lidia Schapira, Steven Come, Virginia Borges, Tamara Cadet, Peter Maramaldi, Ann H. Partridge. The psychosocial impact of caregiving on partners of young women with breast cancer in treatment [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-08.

Abstract Background: NET is offered to postmenopausal patients (pts) with clinical stage 2/3 ER+/HER2- BC to promote breast-conserving surgery. Also limited surgical accessibility during the COVID19 pandemic has increased NET utility. Inability to identify ET-resistant disease at diagnosis risks disease progression (PD) and delays more effective treatments. Dowsett et al. recently demonstrated that baseline levels of ER, progesterone receptor (PR), Ki67 (&gt;15% vs ≤15%), and Ki67 (&gt;10% vs ≤10%) 2-4 weeks (wks) after starting NET may improve appropriate patient (pt) selection for NET (PMC7280290). The ER, PR and Ki67-based prediction model divides pts with primary ER+/HER2- BC into 3 groups for appropriateness for NET: (Group 1) NET is likely to be inappropriate (Allred ER &lt;6 or ER 6 and PgR &lt;6), (Group 2) NET may be appropriate and a biopsy for on-treatment Ki67 analysis may be considered after 2-4 wks of NET (2A: ER 7 or 8 and PgR &lt;6 and 2B: ER 6 or 7 and PgR ≥6) given that on-treatment Ki67 &gt;10% has been associated with worse outcome (PMC5455353), or (Group 3) NET is appropriate (ER 8 and PgR ≥6). The ALTERNATE trial (NCT01953588) randomized postmenopausal women with clinical stage II or III, ER+ (Allred score 6-8)/HER2- BC to receive anastrozole (ANA), fulvestrant (FUL), or ANA + FUL for 6 months, unless Ki67 was &gt;10% on wk 4 or 12 biopsy, in which case pts were triaged to receive neoadjuvant chemotherapy (NCT) or surgery. As previously reported, the ET-sensitive disease (mPEPI 0 plus pCR) rates were similar across the treatment arms and overall 22% (286 of 1,299) pts had Ki67 &gt;10% at wk 4 or 12. The ALTERNATE trial therefore provides a large independent data set to evaluate the NET appropriateness model. Results: Among 1,299 eligible pts randomized to receive 6 months of NET, 214 were excluded due to absent HR Allred score (n=41) or absence of pre-treatment and wk 4 Ki67 determinations (n=173). The proportions of the remaining 1,085 pts in Group 1, 2 and 3 were 1% (n=10), 43% (n= 468), and 56% (n=607), respectively. On-study Ki67 &gt;10% prompting conversion from NET to NCT/Surgery occurred in: Group 1 90% (9 of 10), Group 2 30% (141 of 468), and Group 3 17% (104 of 607) (Table 1). Among the 1,075 pts in Groups 2 and 3, 260 (24%) pts had Ki67 ≤15% at baseline (BL), among whom only 14 (5.4%) had Ki67 &gt;10% at wk 4, compared to 231 of the 815 (28.3%) who had BL Ki67 &gt;15% and subsequent Ki67 &gt;10% at wk 4. 2% of pts who remained on NET due to on-treatment Ki67 &lt;10% had PD. Response and PEPI-0 rates by group will be reported. Conclusion: ALTERNATE trial data support a model whereby levels of ER, PR and Ki67 at diagnosis can be used for the identification of postmenopausal pts with primary ER+/HER2- BC who are appropriate for NET. When baseline ER Allred scores are &gt;6 and Ki67 ≤15%, there is a low likelihood of ET-resistant disease. When BL Ki67 is &gt;15%, ET sensitivity is variable, and on-treatment biopsy for Ki67 may assist in triaging regarding NET appropriateness, particularly given the extremely low local PD rates seen in ALTERNATE when on-treatment Ki67 was &lt;10%. Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG); NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org; Clinical Trials.gov Identifier: NCT01953588 Table 1 Baseline levels of ER, PR, and Ki67 in Relation to Wk 4 Ki67 (N=1,085)BaselineWeek 4GroupNERAllred ScorePRAllred ScoreKi67Ki67 ≤10%N (%)Ki67 &gt;10%N (%)1N=26&lt;6≤15%0 (0%)2 (100%)9 (90)N=86&lt;6&gt;15%1 (12.5%)7 (87.5%)2AN=647 or 8&lt;6≤15%61 (95.3%)3 (4.7%)90 (30.1)N=2357 or 8&lt;6&gt;15%148 (63%)87 (37%)2BN=466 or 7≥6≤15%42 (91.3%)4 (8.7%)51 (30.2)N=1236 or 7≥6&gt;15%76 (61.8%)47 (38.2%)3N=1508≥6≤15%143 (95.3%)7 (4.7%)104 (17.1)N=4578≥6&gt;15%360 (78.8%)97 (21.2%) Citation Format: Matthew J Ellis, Vera Suman, A. Marilyn Leitch, Souzan Sanati, Kiran Vij, Gary W Unzeitig, Jeremy Hoog, Mark Watson, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erika Crouch, Horacio Maluf, Mitch Dowsett, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Travis Dockter, Jo Anne Zujewski, Anna Weiss, Clifford Hudis, Eric P Winer, Kelly Hunt, Ann H Partridge, Cynthia X Ma, Lisa A Carey. Validation of a predictive model for potential response to neoadjuvant endocrine therapy (NET) in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC): An ALTERNATE trial analysis (Alliance A011106) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD2-10.

Abstract Background: Young age at diagnosis is an independent risk factor for recurrence and death from breast cancer (BC), with the greatest impact of young age demonstrated in hormone receptor positive (HR+) disease. Younger women are less likely to be adherent to endocrine therapy (ET), which may contribute to disparate outcomes. Methods: As part of a prospective cohort that enrolled women with BC diagnosed at age ≤40 between 2006-2016, we identified women with HR+, Stage I-III BC. Serial surveys with items assessing socio-demographic and treatment information including medication use are administered 1-2 times per year. Medical record review was used to ascertain stage and HR status and to confirm recurrent disease (locoregional, distant, or new primary breast cancer). Women who initiated ET but discontinued it &lt;5-years post-diagnosis without resumption were classified as non-persistent. Univariable and multivariable regression models were fit to identify predictors of non-persistence and recurrence.Results: Among 607 women who initiated ET (median age at diagnosis: 36, range:17-40; 38%, 45%, 17% were Stage 1, 2, and 3, respectively).16% (99/607) were non-persistent, of whom 30% (30/99) discontinued ET ≤2 years post-diagnosis and over half had discontinued (54%, 54/99) by 3 years. In multivariable regression, those who were younger at diagnosis (age ≤30 vs. 36-40: OR: 3.39, 95% CI: 1.84-6.24; age 31-36 vs. 36-40: OR: 2.81 95% CI: 1.70-4.64) were more likely to discontinue ET while those with a higher stage at diagnosis were less likely to discontinue ET (Stage 2 vs. 1: OR: 0.46, 95% CI: 0.29-0.74; Stage 3 vs 1: OR: 0.32, 95% CI: 0.15-0.68). At a median follow-up time from diagnosis of 7.8 years (range 1-13 years), 15% of women (88/607) recurred or developed a new primary BC at a median time from diagnosis of 3.5 years (range 1-12 years). Of these, 66% (58/88) were distant recurrences, 32% (28/88) loco-regional, and 2% (2/88) new primary BCs. Rates of recurrence were higher among women who were persistent (81/508, 16%) vs. non-persistent (7/99, 7%, p=0.02). In multivariable regression, those who were non-persistent were less likely to recur (OR: 0.43, 95% CI: 0.19-0.98) while those with a higher stage were more likely to recur (Stage 3 vs. 1: OR: 2.36, 95% CI: 1.03-5.41). Sociodemographic, patient, and other treatment factors did not predict recurrence. Conclusions: Approximately 16% of young women with HR+ BC stop ET earlier than indicated, however non-persistence was not a risk factor for BC recurrence a median of 8 years following diagnosis in our cohort. Importantly, women with higher risk disease who are likely to benefit most from adherence to ET were less likely to discontinue treatment. Extended follow-up will further inform the impact of non-persistence on the incidence of late recurrences for which women with HR+ BC are at increased risk. Citation Format: Shoshana M Rosenberg, Yue Zheng, Philip Poorvu, Kathryn Ruddy, Rachel Gaither, Rulla Tamimi, Lidia Schapira, Jeffrey Peppercorn, Steven Come, Virginia Borges, Ann Partridge. Endocrine therapy non-persistence and recurrence in young women with early stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD2-08.

Abstract Background: Ki67 values &gt;10% 2-4 weeks (wks) after starting neoadjuvant ET (NET) indicates persistent cell proliferation, resistance to ET, and is associated with increased risk of recurrence. The ACOSOG Z1031 trial suggested that these tumors are also relatively chemotherapy (chemo) resistant with a low pathologic complete response (pCR) rate to NCT. The ALTERNATE trial (NCT01953588) is a randomized study of neoadjuvant anastrozole (ANA), fulvestrant (FUL), or ANA + FUL in postmenopausal patients (pt) with newly diagnosed clinical stage II or III ER+ (Allred score 6-8)/HER2- BC. Ki67 &gt;10% at wk 4 or 12 after starting NET triggered triage to NCT of physician choice or weekly paclitaxel. Pts who refused protocol-directed therapy, were not candidates for NCT, or decided to undergo immediate surgery are being followed per protocol. Here we report the rates of pCR and residual cancer burden (RCB) following NCT for pts triaged to NCT due to Ki67 &gt;10% at wk 4 or 12. Results: Of the 1,299 eligible pts randomized to receive ANA, FUL, or ANA + FUL, 286 (22%) had Ki67 &gt;10% at wk 4 or 12. 168 of these 286 pts (58.7%) chose to switch to NCT, 32 went to surgery (11.2%), and 86 discontinued further protocol-directed therapy (30.1%). Among the 168 pts who underwent NCT, the presenting clinical T stages were cT2 (n=113; 67.26%), cT3 (n=47; 27.98%) and cT4 (n=8; 4.76%) and N stages were cN0 (n=82; 48.8%), cN1 (n=75; 44.6%), cN2/3 (n=9; 5.4%) and cNx (n=2; 1.2%). Central ER testing was performed on pre-treatment biopsies and confirmed ER Allred score 6-8 in 155 of 168 (92.2%) pts, with the rest being ER Allred score 4-5 (n=5; 3%), ER- (Allred score 0) (n=2; 1.2%), or not tested (n=6; 3.6%). Most (n=139; 82.7%) were ER+/PR+, while 17.3% (n=29) were ER+/PR-, and tumor grades were G1 (n=10; 6%), G2 (n=99; 58.9%), G3 (n=54; 32.1%), not reported (n=5; 3%). Baseline Ki67 levels prior to NET were &gt;10% in 94% (n=158), ≤10% in 3% (n=5), and not done in 3% (n=5). NCT regimens administered included doxorubicin/cyclophosphamide (AC) followed by paclitaxel (T) (n=60; 35.71%); weekly paclitaxel (n=56; 33.33%), docetaxel/cyclophosphamide (TC) (n=33; 19.65%), other doxorubicin and/or taxane containing regimen (n=17; 10.12%), and cyclophosphamide/methotrexate/fluorouracil (CMF) (n=2; 1.19%). 35 (20.8%) pts did not complete planned course of NCT due to toxicity (n=27) or refusal (n=8). 154 NCT pts underwent surgery (mastectomy in 40.3%, and breast conserving surgery in 59.7%). The path ypT stages were Tis/0 (n=10; 6.5%), T1 (n=62; 40.3%), T2 (n=61; 39.6%), and T3/4 (n=21; 13.6%), and the ypN stages were N0 (n=66; 42.9%), N1 (n=57; 37%), N2/3 (n=30; 19.5%), and Nx (n=1; 0.6%). Among the 168 pts who started on NCT (intent to treat population), there were 8 pCRs (no invasive disease in the breast or lymph nodes) (4.8%; 95% CI: 2.1% to 9.2%). Residual Cancer Burden (RCB) categories include RCB 0 (n=8; 4.8%), RCB 1 (n=15; 8.9%), RCB 2 (n=82; 48.8%), RCB 3 (n=42; 25.0%), and not determined (n=21; 12.5%). Correlations of baseline pt and tumor characteristics with pathology response to NCT will also be presented. Conclusion: In pts with NET-resistant ER+/HER2- BC, salvage NCT is not likely to induce a complete or near complete response. More effective treatments are needed for this high-risk ER+/HER2- pt population. Support: U10CA180821, U10CA180882, U24CA196171, UG1CA189856, U10CA180868 (NRG); NCI BIQSFP, BCRF, Genentech, AstraZeneca. https://acknowledgments.alliancefound.org. Clinical Trials.gov Identifier: NCT01953588 Citation Format: Cynthia X Ma, Vera Suman, A. Marilyn Leitch, Souzan Sanati, Kiran Vij, Gary W Unzeitig, Jeremy Hoog, Mark Watson, Olwen Hahn, Joseph Guenther, Abigail Caudle, Erika Crouch, Horacio Maluf, Amy Tiersten, Monica Mita, Wajeeha Razaq, Tina J Hieken, Yang Wang, Travis Dockter, Jo Anne Zujewski, Anna Weiss, Kelly Hunt, Clifford Hudis, Eric P Winer, Matthew J Ellis, Lisa A Carey, Ann H Partridge. Neoadjuvant chemotherapy (NCT) response in postmenopausal women with clinical stage II or III estrogen receptor positive (ER+) and HER2 negative (HER2-) breast cancer (BC) resistant to endocrine therapy (ET) in the ALTERNATE trial (Alliance A011106) [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS4-05.

Abstract Background: Pregnancy-related issues are a priority for young breast cancer (BC) patients. Increasing evidence has shown that pregnancy after prior BC diagnosis is feasible. Nevertheless, few BC survivors conceive following anticancer treatment completion and many physicians remain concerned about the potentially detrimental effects of pregnancy after BC in terms of fetal/obstetrical outcomes and maternal prognosis. This systematic review and meta-analysis aims at providing updated and solid evidence on these important issues. Methods: A systematic literature review up to January 31, 2020 with no language restriction was conducted to identify studies including patients with a pregnancy after prior BC diagnosis. Chances of pregnancy after BC, fetal and obstetrical outcomes, disease-free survival (DFS) and overall survival (OS) were assessed. Pooled relative risks (RRs), hazard ratios (HRs) or odds ratio (ORs) with 95% confidence intervals (CI) were calculated using the random effects models. The study is registered with the PROSPERO registration number CRD42020158324. Results: Overall, 39 studies were included. Out of the 8,265,713 young women included in these studies, 8,093,401 were from the general population, 57,739 had cancers other than BC, 114,573 had BC. Among the 114,573 BC patients, 7,505 had a pregnancy after BC diagnosis and 107,068 did not. Compared to women from the general population, BC patients had 60% reduced chances of having a pregnancy following anticancer treatment completion (RR 0.40, 95% CI 0.32-0.49). Among other cancer patients, only women with prior cervical cancer had lower pregnancy rates (RR 0.33, 95% CI 0.31-0.35) than BC patients. Compared to the general population, BC survivors had significantly increased risks of low birth weight (OR 1.50, 95% CI 1.31-1.73), small for gestational age (OR 1.16, 95% CI 1.01-1.33), preterm delivery (OR 1.45, 95% CI 1.11-1.88) and caesarean section (OR 1.14, 95% CI 1.04-1.25). No significant increased risk of congenital abnormalities (OR 1.63, 95% CI 0.89-2.98) or other pregnancy or delivery complications (spontaneous or induced abortion, gestosis, antepartum or postpartum hemorrhage) was observed. Prior chemotherapy exposure or short pregnancy interval (defined as &lt;2 or &lt;5 years after BC diagnosis) were not associated with additional increased risk of complications. Pregnancy after BC was not associated with a negative impact on patients’ outcomes. Compared to BC patients without subsequent pregnancy, those with pregnancy after BC had better OS (HR 0.56, 95% CI 0.46-0.67) and DFS (HR 0.73, 95% CI 0.56-0.94). Similar results were observed in the studies correcting for the potential “healthy mother effect” (OS: HR 0.52, 95% CI 0.42-0.65; DFS: HR 0.74, 95% CI 0.58-0.96). No detrimental prognostic effect of pregnancy after BC was observed in patients with hormone-receptor positive disease (DFS: HR 1.10, 95% CI 0.73-1.66), while better outcomes were observed for those with hormone-receptor negative disease (DFS: HR 0.72, 95% CI 0.55-0.95). The safety of pregnancy after BC was observed irrespective of BRCA status, nodal status, previous chemotherapy exposure, pregnancy interval and pregnancy outcomes. Conclusions: This large meta-analysis provides solid evidence on the safety of pregnancy after prior BC diagnosis. The increased risk of fetal and obstetrical complications (but not of congenital abnormalities) calls for ensuring a closer monitoring of these pregnancies. The significantly reduced chances of conceiving as compared to the general population and other cancer patients should raise further awareness on the need to improve the oncofertility counseling of young BC patients wishing to complete their family planning following anticancer treatment completion. Citation Format: Eva Blondeaux, Marta Perachino, Marco Bruzzone, Richard A. Anderson, Evandro De Azambuja, Philip D. Poorvu, Hee Jeong Kim, Cynthia Villarreal-Garza, Barbara Pistilli, Ines Vaz-Luis, Cristina Saura, Kathryn J. Ruddy, Maria Alice Franzoi, Chiara Sertoli, Marcello Ceppi, Hatem A. Azim, Jr., Frederic Amant, Isabelle Demeestere, Lucia Del Mastro, Ann H. Partridge, Olivia Pagani, Fedro A. Peccatori, Matteo Lambertini. Chances of pregnancy after breast cancer, reproductive and disease outcomes: A systematic review and meta-analysis [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr GS3-09.

Objective: We aimed to investigate eligibility for breast conserving surgery (BCS) pre- and post-neoadjuvant systemic therapy (NST), and trends in the surgical treatment of young breast cancer patients. Background: Young women with breast cancer are more likely to present with larger tumors and aggressive phenotypes, and may benefit from NST. Little is known about how response to NST influences surgical decisions in young women. Methods: The Young Women's Breast Cancer Study, a multicenter prospective cohort of women diagnosed with breast cancer at age ≤40, enrolled 1302 patients from 2006 to 2016. Disease characteristics, surgical recommendations, and reasons for choosing mastectomy among BCS-eligible patients were obtained through the medical record. Trends in use of NST, rate of clinical and pathologic complete response, and surgery were also assessed. Results: Of 1117 women with unilateral stage I-III breast cancer, 315 (28%) received NST. Pre-NST, 26% were BCS eligible, 17% were borderline eligible, and 55% were ineligible. After NST, BCS eligibility increased from 26% to 42% (P < 0.0001). Among BCS-eligible patients after NST (n = 133), 41% chose mastectomy with reasons being patient preference (53%), BRCA or TP53 mutation (35%), and family history (5%). From 2006 to 2016, the rates of NST (P = 0.0012), clinical complete response (P < 0.0001), and bilateral mastectomy (P < 0.0001) increased, but the rate of BCS did not increase (P = 0.34). Conclusion: While the proportion of young women eligible for BCS increased after NST, many patients chose mastectomy, suggesting that surgical decisions are often driven by factors beyond extent of disease and treatment response.

BackgroundMany young women with newly diagnosed breast cancer are interested in future pregnancies. Prospective data regarding fertility interest and reproductive patterns after diagnosis are needed to counsel patients.MethodsThe Young Women's Breast Cancer Study is a multicenter, prospective cohort of women who were diagnosed with breast cancer at age ≤40 years between 2006 and 2016. Women complete surveys at baseline, every 6 months for 3 years, then annually. Here, the authors describe fertility interest and pregnancies within 5 years of diagnosis for women with stage 0 through III breast cancer.ResultsOf 1026 eligible participants, 368 (36%) reported interest in future biologic children at least once within 5 years after diagnosis, including 16% at 5 years after diagnosis. Among 130 women who attempted to become pregnant, 90 (69.2%) conceived; and, among 896 women who did not attempt to conceive, 18 (2.0%) became pregnant, with a total of 152 pregnancies resulting in 91 live births. Factors associated with pregnancy included younger versus older age at diagnosis (aged ≤30 vs 36‐40 years: odds ratio [OR], 6.63; 95% CI, 3.18‐13.83; P < .0001; aged 31‐35 vs 36‐40 years: OR, 5.86; 95% CI, 3.37‐10.17; P < .0001) and being nulliparous versus parous (OR, 2.66; 95% CI, 1.56‐4.53; P = .001). The receipt of endocrine therapy versus no endocrine therapy (OR, 0.35; 95% CI, 0.20‐0.59; P = .001) was inversely associated with pregnancy.ConclusionsMany women remain interested in future fertility in the 4 years after a breast cancer diagnosis, indicating that longitudinal fertility discussions are needed. Although a minority of those interested in having children attempted to become pregnant in the first 5 years, most who attempted to conceive did so and had live births.

Abstract Antimullerian hormone (AMH) is a promising biomarker for ovarian reserve. In this study, we assessed AMH before and 1 year after initiation of adjuvant chemotherapy on National Surgical Adjuvant Breast and Bowel Project (NSABP)/NRG Oncology B-47 in female participants aged 42 years and younger (median age = 39 years). At baseline, median AMH was 1.2 ng/mL; 13 (4.7%) values were less than 0.1 ng/mL (the threshold for detectable levels, in the perimenopause and menopause range), and 57 values (20.6%) were less than 0.5 ng/mL. At 1 year, 215 (77.6%) were less than 0.1 ng/mL, and 264 (95.3%) were less than 0.5 ng/mL. Postchemotherapy menses were reported by 46.2% of participants. Multivariable logistic regression found that the odds of having postchemotherapy menses increased with younger age, higher body mass index, and higher prechemotherapy AMH, but not by trastuzumab administration or by the choice of chemotherapy (doxorubicin-cyclophosphamide followed by paclitaxel vs docetaxel-cyclophosphamide). We conclude that higher prechemotherapy AMH predicts a lower risk of chemotherapy-induced amenorrhea and that AMH 1 year after chemotherapy initiation is not informative in this setting because it is likely to be very low.