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Abstract PD6-1: BREAST-Q satisfaction and quality of life outcomes in young women undergoing mastectomy and reconstruction for breast cancer
Dominici, Laura S. , Hu, Jiani , Kim, Hee Jeong , King, Tari A. , Ruddy, Kathryn J. , Peppercorn, Jeffrey , Schapira, Lidia , Come, S, Wong, Julia S., Partridge, Ann, Rosenberg, Shoshana, Tamimi, Rulla M. , Borges, Virginia F. , Warner, Ellen

Cancer Research | March 26, 2020 | Volume: 80 | Issue: 4_Supplement | Pages: PD6-1-PD6-1

10.1158/1538-7445.sabcs19-pd6-1 Get It

Abstract Background: Young women with breast cancer (BC) often receive aggressive local therapy and are more likely to undergo (bilateral) mastectomy and receive postmastectomy radiation (RT) than older women. Our previous work suggested better quality of life (QOL) outcomes among women undergoing breast conserving therapy (BCT) vs. mastectomy, even with reconstruction (recon), although limited data was available regarding recon. In the current analysis, we sought to understand the impact of recon, accounting for RT, on long-term satisfaction and QOL. Methods: Between 10/2016-11/2017, we administered the BREAST-Q, a validated patient-reported outcomes measure designed to evaluate satisfaction and QOL after breast cancer surgery and recon, to 743 women in the Young Women’s Breast Cancer Study, a multi-site prospective cohort that enrolled women diagnosed (dx’d) at age < 40 from 2006-2016. Demographic and treatment information was obtained by surveys and chart review. Recon was defined as autologous, implant or complex (combination of autologous and implant). Mean BREAST-Q scores for each domain (breast satisfaction, physical, psychosocial, and sexual) were compared by recon types and stratified by receipt of RT; higher BREAST-Q scores (range: 0-100) indicate better QOL. Linear regression was used to identify predictors of BREAST-Q scores. Results: 584 women with Stage 0-3 BC completed the Breast-Q at a median of 5.7 [range 2-10] years from dx), 357 (61%) had mastectomy and recon and were included in the analytic sample. Median age at dx was 36 years; 85% had stage 0, 1 or 2 disease; 41% received RT and 76% underwent bilateral mastectomy. 90.5% underwent immediate recon; of which 65.5% were tissue expander placement. Definitive recon included autologous tissue in 16%; implants in 81% and complex recon in 3%. Mean BREAST-Q breast satisfaction, psychosocial, and physical well-being scores differed based on recon type accounting for RT (Table 1). Significantly lower scores for breast satisfaction were seen in women having implant +RT. Scores were not impacted by bilateral procedure, timing of recon, use of tissue expander, extent of axillary surgery, cancer stage or other treatment factors. In multivariate analyses, receipt of RT, lymphedema and implant-based recon were associated with lower breast satisfaction scores. Physical well-being scores were lower for those with complex recon, for non-White women, for women who reported being financially uncomfortable, for those with lymphedema, and for those <5 years from surgery. Psychosocial well-being scores were lower for women who received RT, had BMI >25, and for those who reported being financially uncomfortable. Sexual well-being scores were lower for women with a BMI >25 and for those who reported being financially uncomfortable. Conclusion Type of recon and receipt of radiation among young survivors who undergo mastectomy and recon for early breast cancer appears to have a differential impact on satisfaction and QOL. Our finding of lower breast satisfaction among young women who received RT, particularly after implant recon, underscores the importance of counseling regarding surgical options, especially for women who may receive RT after mastectomy and who are candidates for BCT. Table 1. Unadjusted BREAST-Q scores stratified by RTBREAST-Q DomainAutologous -RT N=29Autologous +RT N=27Implant -RT N=174Implant +RT N=113Complex N=13Global p-valueSatisfaction with Breasts, mean (sd)67 (19)63 (18)64 (18)53 (18)58 (22)<0.01Physical well-being, mean (sd)81 (13)80 (14)80 (15)77 (14)67 (18)0.01Psychosocial well-being, mean (sd)71 (18)64 (18)72 (20)66 (23)62 (20)0.03Sexual well-being, mean (sd)54 (21)50 (24)52 (20)47 (22)48 (27)0.26RT= radiation Citation Format: Laura Dominici, Jiani Hu, Hee Jeong Kim, Tari King, Kathryn Ruddy, Rulla Tamimi, Jeffrey Peppercorn, Lidia Schapira, Virginia Borges, Stephen Come, Ellen Warner, Julia Wong, Ann Partridge, Shoshana Rosenberg. BREAST-Q satisfaction and quality of life outcomes in young women undergoing mastectomy and reconstruction for breast cancer [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 PD6-1.
Abstract P5-08-07: Tobacco use, alcohol consumption, and breast cancer somatic genomic alterations
Heng, Yujing J. , Hankinson, Susan E. , Wang, Jun , Andrade, Victor Piana de , Brufsky, Adam , King, Tari A. , Vachon, Celine M. , Brufsky, Adam M , Hankinson, Susan E. , Alexandrov, Ludmil B. , Ambrosone, Christine B. , Couch, Fergus J. , Modugno, Francesmary , Vachon, Celine M. , Eliassen, A. Heather , Tamimi, Rulla M. , Kraft, Peter

Cancer Research | March 26, 2020 | Volume: 80 | Issue: 4_Supplement | Pages: P5-08-07-P5-08-07

10.1158/1538-7445.sabcs19-p5-08-07 Get It

Abstract Background: Understanding the molecular influence of epidemiological risk factors can provide insights into breast cancer etiology and progression, and lead to better prevention efforts and treatment guidelines. The link between modifiable breast cancer risk factors and tumor genomic alterations remains unexplored. This study evaluated the association of tobacco use and alcohol consumption with somatic copy number variation (SCNV), total somatic mutation burden (TSMB), seven single base substitution (SBS) signatures (SBS1, SBS2, SBS3, SBS5, SBS13, SBS29, and SBS30) (1-3), and nine breast cancer driver mutations (CDH1, GATA3, KMT2C, MAP2K4, MAP3K1, NCOR1, PIK3CA, RUNX1, and TP53) (4,5), in a subset of The Cancer Genome Atlas (TCGA). Method: Clinical and genomic data were retrieved from the TCGA database, and breast cancer risk factor information was collected from four TCGA sites; in all, 219 female breast cancer cases were included. Pre-diagnostic tobacco use was defined as never or ever; alcohol consumption was defined as drinkers or non-drinkers. Total SCNV was obtained by summing all segments with ≥|0.2|. TSMB was calculated by summing all significant mutations for each case. SBS signatures were computed using whole exome sequencing data. Analyses were conducted in all tumors (i.e., pooled) and by stratifying according to estrogen receptor (ER) status using multivariate regression, adjusting for co-variables. Results: Tobacco users had higher TSMB compared to non-users (p<0.05 all tumors). Alcohol drinkers had higher SCNV compared to non-drinkers (p<0.05 all tumors and among ER+ tumors). Tobacco use was not associated with any SBS signature. SBS3 signature (defective homologous recombination-based repair) was exclusively found in alcohol drinkers with ER- disease. No breast cancer driver mutation was associated with tobacco use or alcohol consumption. Conclusion: This study provides preliminary evidence that tobacco use and alcohol consumption can influence breast tumor biology, in particular, DNA alterations. Future larger epidemiological studies are required to confirm these findings. References 1. Vineis P, et al. Mutational signatures associated with tobacco smoking in human cancer. Science. 2016;354(6312):618-22. 2. Alexandrov LB, et al. Clock-like mutational processes in human somatic cells. Nat Genet. 2015;47(12):1402-7. 3. Petljak M, Alexandrov LB. Understanding mutagenesis through delineation of mutational signatures in human cancer. Carcinogenesis. 2016;37(6):531-40. 4. Heng YJ, et al. The molecular basis of breast cancer pathologic phenotypes. J Pathol. 2017 Nov;241(3):375-91. 5. Ciriello G, et al. Comprehensive Molecular Portraits of Invasive Lobular Breast Cancer. Cell. 2015 Oct 10;163(2):506-19. Citation Format: Yujing J Heng, Susan E Hankinson, Jun Wang, Ludmil B Alexandrov, Christine B Ambrosone, Victor Piana de Andrade, Adam M Brufsky, Fergus J Couch, Tari A King, Francesmary Modugno, Celine M Vachon, A. Heather Eliassen, Rulla M Tamimi, Peter Kraft. Tobacco use, alcohol consumption, and breast cancer somatic genomic alterations [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 P5-08-07.
Abstract P4-07-02: Clinicopathological features and BRCA 1/2 status in a large prospective cohort of young women with breast cancer
Rosenberg, Shoshana M. , Poorvu, Philip D. , Ruddy, Kathryn J. , Kirkner, Greg, Peppercorn, Jeffrey , Schapira, Lidia , Come, Steven E. , Brachtel, Elena F. , Collins, Laura C. , Guzmán‐Arocho, Yaileen D. , Snow, Craig , Tamimi, Rulla M. , Borges, Virginia F. , Warner, Ellen , Partridge, Ann H.

Cancer Research | March 26, 2020 | Volume: 80 | Issue: 4_Supplement | Pages: P4-07-02-P4-07-02

10.1158/1538-7445.sabcs19-p4-07-02 Get It

Abstract Background: Breast cancer arising in young women is more likely to have higher risk features than in older women and more likely to be associated with germline BRCA1 or BRCA2 mutations. We previously reported a higher distribution of luminal B-like tumors among young women. Here we present the clinical and pathologic features of invasive disease in a large prospective cohort of young women with breast cancer, and associations between surrogate molecular subtype and BRCA 1/2 mutation status. Methods: Among 1,297 young women (aged ≤40 years) with breast cancer enrolled from 2006-2016, tumor histopathological features were examined by central review, and biomarker status was extracted from pathology reports. Based on histologic grade and biomarker expression, invasive tumors were categorized as luminal A-like (LA=ER/PR+ and HER2-, histologic grade 1 or 2), luminal B-like (LB=ER/PR+ and HER2+, or ER/PR+, HER2-, and grade 3), HER2 enriched (E) (ER/PR- and HER2+) or triple negative (TN=ER-, PR- and HER2-). Tumor stage, clinical characteristics, and BRCA status were retrieved by medical record review (and patient survey for BRCA status if not in medical record). Results: The majority of women presented with early stage invasive disease (8% stage 0, 32% stage 1, 40% stage 2, 15% stage 3; 5% stage 4). Among invasive tumors with evaluable molecular phenotype (n=1,136), 57% were high grade and the distribution of subtypes was: 33% LA, 42% LB, 8% HER2E, and 16% TN (Table 1). Among different age groups (≤ 30, 31-35, and 36-40 years), there were no significant differences in molecular phenotype, tumor stage, tumor grade or histopathological features including presence of tumor necrosis, lymphocytic infiltration, and central fibrotic focus. 96% of women were tested for BRCA1 and BRCA2 germline mutations, and 127 (11%) tested positive: 65% were BRCA1+, and 35% were BRCA2+ (table 2). Among BRCA1+ patients, 2% of cancers were LA, 30% LB, 5% HER2E, and 62% TN; among BRCA2+, 29% were LA, 56% LB, 2% HER2E, and 13% TN. These proportions were relatively consistent across age groups. BRCA1+ patients’ tumors were proportionately more TN and BRCA2+ patients’ tumors more likely to be LB/HER2 negative (p<0.0001), irrespective of age category. Conclusion: In a large cohort of women diagnosed with breast cancer at age ≤40, there was no association between age group (≤ 30, 31-35, vs. 36-40 years) and tumor stage, grade, or tumor molecular phenotype among women with invasive disease. As in older women, tumor molecular phenotype does vary by BRCA1 or BRCA2 mutation status, which has implications for prevention and treatment. Table 1. Subtype by age groupTotal (n=1136)≤30 yrs (n=144)31-35 yrs (n=314)36-40 yrs (n=678)p=0.42Luminal A-like377 (33%)48 (33%)99 (32%)230 (34%)Luminal B-like477 (42%)59 (41%)137 (44%)281 (41%)• ER/PR+, HER2-, grade 3245 (22%)27 (19%)68 (22%)150 (22%)• ER/PR+, HER2+232 (20%)32 (22%)69 (22%)131 (19%)HER2E95 (8%)13 (9%)34 (11%)48 (7%)Triple Negative187 (16%)24 (17%)44 (14%)119 (18%) Table 2. Subtype by BRCA statusTotal(n=1136)BRCA1+(n=82)BRCA2+(n=45)No mutation/not tested(n=1009)p<0.0001Luminal A-like377 (33%)2 (2%)13 (29%)362 (36%)Luminal B-like477 (42%)25 (30%)25 (56%)427 (42%)• ER/PR+, HER2-, grade 3245 (22%)21 (26%)18 (40%)206 (20%)• ER/PR+, HER2+232 (20%)4 (5%)7 (16%)221 (22%)HER2E95 (8%)4 (5%)1 (2%)90 (9%)Triple Negative187 (16%)51 (62%)6 (13%)130 (13%) Citation Format: Yaileen D Guzman-Arocho, Shoshana M. Rosenberg, Philip Poorvu, Kathryn J. Ruddy, Greg Kirkner, Craig Snow, Rulla M. Tamimi, Jeffrey Peppercorn, Lidia Schapira, Virginia F. Borges, Steven E. Come, Elena F. Brachtel, Ellen Warner, Ann H. Partridge, Laura C. Collins. Clinicopathological features and BRCA 1/2 status in a large prospective cohort of young women with breast cancer [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 P4-07-02.
Body weight changes in young breast cancer survivors and associated predictors.
Sella, Tal , Tan‐Wasielewski, Zhenying, Rosenberg, Shoshana M. , Poorvu, Philip D. , Ruddy, Kathryn J. , Gelber, Shari , Schapira, Lidia , Come, Steven E. , Peppercorn, Jeffrey , Ligibel, Jennifer A. , Tamimi, Rulla M. , Borges, Virginia F. , Partridge, Ann H.

Journal of Clinical Oncology | March 12, 2020 | Volume: 37 | Issue: 15_suppl | Pages: 11574-11574

10.1200/jco.2019.37.15_suppl.11574 Get It

11574 Background: Weight gain after cancer diagnosis is common in cancer survivors and has been linked to increased treatment toxicity, poor quality of life, and increased risk of second cancers and overall mortality. Young breast cancer (BC) survivors may be especially susceptible to weight changes given the impact of treatments such as chemotherapy and hormonal therapy on menopausal status. Methods: We identified women with Stage 0-III breast cancer diagnosed at ≤40 years (y) between 2006-2016 from a multi-center prospective cohort study. Clinical data including self-reported pre-diagnosis and follow-up weights were obtained using baseline and follow-up patient surveys. Participants missing baseline weight, pregnant at diagnosis/within 1y of diagnosis or with BC recurrence within 1y were excluded; those pregnant or with BC recurrence between 1-3y from diagnosis were excluded from the 3y analysis. Menopausal status at baseline and treatment-related amenorrhea (TRA) in follow-up were defined by self-reported last menstrual period. Factors associated with weight gain (>5%) were evaluated using univariate two-sided Fisher's exact test. Results: At baseline, 1y and 3y post diagnosis, 956, 899 and 687 women were eligible for analysis respectively. Median age at diagnosis was 37y (17 - 40), 65% received endocrine therapy and 74% chemotherapy. Premenopausal status was verified in 94% at baseline. Mean BMI at baseline was 24.4 (SD 5.3) kg/m2; 20% (187/956) were overweight and 12% (116/956) obese. At 1y and 3y, mean BMI increased modestly to 24.7 (SD 5.6) and 24.9 (SD 5.2), respectively with weight gain (>5%) observed in 18% (164/899) and 13% (87/687) respectively. 37% (300/804) and 32% (196/615) of eligible premenopausal subjects experienced TRA at 1y and 3y, respectively. Receipt of chemotherapy, receipt of endocrine therapy and TRA were not associated with weight gain at any timepoint. Conclusions: In this large prospective cohort of young BC survivors, mean BMI increased only modestly over time. Self-reported weight gain was not associated with treatment and not exacerbated by TRA. Further analysis to understand the effects of physical activity and other predictors of weight gain in this population are ongoing.
The Association of Modifiable Breast Cancer Risk Factors and Somatic Genomic Alterations in Breast Tumors: The Cancer Genome Atlas Network
Heng, Yujing J. , Hankinson, Susan E. , Wang, Jun , Alexandrov, Ludmil B. , Ambrosone, Christine B. , Andrade, Victor Piana de , Brufsky, Adam , King, Tari A. , Modugno, Francesmary , Vachon, Celine M. , Eliassen, A. Heather , de Andrade, Victor P , Modugno, Francesmary , Brufsky, Adam M , Ambrosone, Christine B , Eliassen, A Heather , Alexandrov, Ludmil B , Hankinson, Susan E. , Couch, Fergus J. , Vachon, Celine M. , Tamimi, Rulla M. , Kraft, Peter

Cancer Epidemiology, Biomarkers & Prevention | January 13, 2020 | Volume: 29 | Issue: 3 | Pages: 599-605

10.1158/1055-9965.epi-19-1087 | PMID 31932411 Get It

Abstract Background: The link between modifiable breast cancer risk factors and tumor genomic alterations remains largely unexplored. We evaluated the association of prediagnostic body mass index (BMI), cigarette smoking, and alcohol consumption with somatic copy number variation (SCNV), total somatic mutation burden (TSMB), seven single base substitution (SBS) signatures (SBS1, SBS2, SBS3, SBS5, SBS13, SBS29, and SBS30), and nine driver mutations (CDH1, GATA3, KMT2C, MAP2K4, MAP3K1, NCOR1, PIK3CA, RUNX1, and TP53) in a subset of The Cancer Genome Atlas (TCGA). Methods: Clinical and genomic data were retrieved from the TCGA database. Risk factor information was collected from four TCGA sites (n = 219 women), including BMI (1 year before diagnosis), cigarette smoking (smokers/nonsmokers), and alcohol consumption (current drinkers/nondrinkers). Multivariable regression analyses were conducted in all tumors and stratified according to estrogen receptor (ER) status. Results: Increasing BMI was associated with increasing SCNV in all women (P = 0.039) and among women with ER− tumors (P = 0.031). Smokers had higher SCNV and TSMB versus nonsmokers (P < 0.05 all women). Alcohol drinkers had higher SCNV versus nondrinkers (P < 0.05 all women and among women with ER+ tumors). SBS3 (defective homologous recombination-based repair) was exclusively found in alcohol drinkers with ER− disease. GATA3 mutation was more likely to occur in women with higher BMI. No association was significant after multiple testing correction. Conclusions: This study provides preliminary evidence that BMI, cigarette smoking, and alcohol consumption can influence breast tumor biology, in particular, DNA alterations. Impact: This study demonstrates a link between modifiable breast cancer risk factors and tumor genomic alterations.
Prognostic Impact of the 21-Gene Recurrence Score Assay Among Young Women With Node-Negative and Node-Positive ER-Positive/HER2-Negative Breast Cancer
Poorvu, Philip D. , Gelber, Shari , Rosenberg, Shoshana M. , Ruddy, Kathryn J. , Collins, Laura C. , Peppercorn, Jeffrey , Schapira, Lidia , Come, Steven E. , Russell, Christy , Tamimi, Rulla M. , Borges, Virginia F. , Warner, Ellen , Jakubowski, Debbie , Winer, Eric P. , Partridge, Ann H.

Journal of Clinical Oncology | December 6, 2019 | Volume: 38 | Issue: 7 | Pages: 725-733

10.1200/jco.19.01959 | PMID 31809240 Get It

PURPOSE The 21-gene recurrence score (RS) assay is prognostic among women with early-stage estrogen receptor–positive (ER+) and human epidermal growth factor receptor 2–negative (HER2−) breast cancer and is used to inform recommendations for chemotherapy. Women ≤ 40 years of age represent a minority of patients studied using gene expression profiles. METHODS The Young Women's Breast Cancer Study is a prospective cohort of women diagnosed with breast cancer at age ≤ 40 years and enrolled patients between 2006 and 2016 (N = 1,302). We identified patients with stage I-III ER+/HER2− breast cancer. The RS assay was performed on banked specimens for patients who had not been tested clinically. Distant recurrence-free survival (DRFS) was assessed by TAILORx and traditional RS risk groups among patients with axillary node–negative (N0) and limited node–positive (N1) breast cancer. RESULTS Among eligible women (N = 577), 189 (33%) had undergone RS testing, and 320 (56%) had banked specimens sufficient for testing. Median follow-up was 6.0 years. Median age at diagnosis was 37.2 years; 300 of 509 patients (59%) had N0 breast cancer, of whom 195 (65%) had an RS of 11-25 and fewer than half (86 of 195; 44%) received chemotherapy. Six-year DRFS rates were 94.4% and 92.3% (RS < 11), 96.9% and 85.2% (RS 11-25), and 85.1% and 71.3% (RS ≥ 26) among women with N0 and N1 disease, respectively. CONCLUSION The RS assay is prognostic among young women with node-negative and limited node-positive breast cancer, representing a valuable tool for risk stratification. Disease outcomes with a median follow-up of 6 years among young women with N0 disease and an RS of 0-25, a minority of whom received chemotherapy, and node-positive disease with an RS < 11 were very good, whereas those with N0 disease and an RS ≥ 26 or N1 disease with an RS ≥ 11 experienced substantial risk of early distant recurrence.
Diagnostic and treatment delays in young women with breast cancer.
Poorvu, Philip D. , Sella, Tal , Rosenberg, Shoshana M. , Ruddy, Kathryn J. , Gelber, Shari , Peppercorn, Jeffrey , Schapira, Lidia , Come, Steven E. , Zheng, Yue , Tamimi, Rulla M. , Borges, Virginia F. , Warner, Ellen , Partridge, Ann H.

Journal of Clinical Oncology | May 27, 2019 | Volume: 37 | Issue: 15_suppl | Pages: 6575-6575

10.1200/jco.2019.37.15_suppl.6575 Get It

6575 Background: Delays in diagnosis (dx) and treatment (tx) affect breast cancer (BC) outcomes. We sought to identify factors associated with delays among young women, who do not undergo routine screening and often have pregnancy or breastfeeding-related breast changes that may mask a BC. Methods: The Young Women’s Breast Cancer Study is a multicenter, prospective cohort that enrolled 1302 women with newly dx BC age ≤40 between 2006-2016. Women reported the method and timing of cancer detection on the baseline survey. 231 were ineligible or excluded due to missing information. Among those reporting self-detected cancers, using multivariable regression we evaluated factors associated with delays ≥90 days (d) from symptom to presentation (self delay) and presentation to dx (care delay); in stage 0-III BC we evaluated delays ≥60d from dx to tx (tx delay). Results: 1071 eligible women had median age at dx of 37 yrs (17-40) and 74% reported self-detected cancers. Self delay or care delay ≥90d was reported in 17% and 13%, respectively. Factors inversely associated with self delay included pregnancy at dx (vs nulliparous, OR 0.10, CI 0.01-0.78) and perceived financial comfort (vs not, OR 0.62, CI 0.41-0.93). Women dx ≤1 year post-partum who breastfed (vs nulliparous, OR 2.60, CI 1.14-5.93) and those with a family history of breast/ovarian cancer (vs none, OR 1.79, CI 1.00-3.19) were more likely to have a care delay. Age was inversely associated with care delays (OR 0.94, CI 0.89-0.99). Tx delay was reported by 10% (105/1015), and associated with being single (vs partnered, OR 1.61, CI 1.02-2.56 ), non-white (vs white, OR 1.85, CI 1.09-3.13) and having Stage 0 BC (vs stage 1, OR: 3.08, CI 1.65-5.77); women with stage 3 BC (vs stage 1, OR 0.13, CI 0.03-0.56) were less likely to have a tx delay. Conclusions: In this cohort, most young women with BC underwent timely dx and tx initiation. Women dx ≤1 year post-partum who breastfed were more likely to experience a care delay, likely because lactational changes may mask BC signs and symptoms. The associations of perceived financial status with self delay and non-white race with tx delay underscore the need for additional support to ensure timely care for underserved populations with the goal of eliminating disparities in outcomes.
Genomics of HER2+ breast cancer in young women before and after exposure to chemotherapy (chemo) plus trastuzumab (H).
Waks, Adrienne G. , Jain, Esha , Collins, Laura C. , Rosenberg, Shoshana M. , Ruddy, Kathryn J. , Schapira, Lidia , Come, Steven E. , Peppercorn, Jeffrey , Wagle, Nikhil , Tamimi, Rulla M. , Borges, Virginia F. , Warner, Ellen , Snow, Craig , Partridge, Ann H. , Jain, Esha

Journal of Clinical Oncology | May 27, 2019 | Volume: 37 | Issue: 15_suppl | Pages: 554-554

10.1200/jco.2019.37.15_suppl.554 Get It

554 Background: HER2+ breast cancer (BC) is particularly common in young women. Genomic features of HER2+ tumors before and after H-based therapy have not been described in a population of young women and may point to clinically targetable mechanisms of resistance. Methods: From a large prospective cohort of women diagnosed with BC age ≤40 years, we identified those with HER2+ BC and tumor tissue available for sequencing before and after chemo+H. Whole exome sequencing (WES) was performed on each tumor and on germline DNA from blood. Tumor-normal pairs were analyzed for mutations and copy number (CN) changes. Evolutionary analysis was performed for patients with both pre- and post-treatment (tx) samples. Results: 22 women had successful WES samples from at least one timepoint; 13 of these had paired sequencing results both before and after chemo+H. For the majority of women, post-tx sample was following neoadjuvant chemo + H, though post-tx timepoint for other women represented locoregional or distant metastasis (Table). TP53 was the only gene that was significantly recurrently mutated in both pre- and post-tx samples. Comparison of matched pre-tx and post-tx samples demonstrated that large changes in HER2 CN over the course of tx were uncommon, only 2/13 pts had > 2-fold change in HER2 CN. Other clonal and subclonal genomic alterations were found to be acquired in the post-tx sample compared to the pre-tx sample. One patient acquired a putative activating mutation in ERBB2. Another patient acquired a clonal hotpsot mutation in TP53. MYC gene amplification was observed in 4 post-tx tumors. NOTCH2 alterations were found in post-tx biopsies from 2 different patients, and mutations in STIL were also found in post-tx biopsies from 2 patients, though the function of these mutations is not known. Conclusions: HER2+ breast tumors in young women display genomic evolution following tx with chemo+H. HER2 CN changes are uncommon, but we identified several genes that warrant exploration as potential mechanisms of resistance to therapy in this population.[Table: see text]
Nonadherent behaviors among young women on adjuvant endocrine therapy for breast cancer
Wassermann, Johanna , Gelber, Shari , Rosenberg, Shoshana M. , Ruddy, Kathryn J. , Schapira, Lidia , Come, Steven E. , Meyer, Meghan E., Partridge, Ann H. , Partridge, Ann H , Tamimi, Rulla M. , Borges, Virginia F.

Cancer | May 23, 2019 | Volume: 125 | Issue: 18 | Pages: 3266-3274

10.1002/cncr.32192 | PMID 31120571 Get It

Background Young age is a known factor associated with suboptimal adherence to endocrine therapy (ET) for adjuvant breast cancer (BC) treatment. This study was aimed at assessing nonadherent behaviors and associated factors among young women with early‐stage hormone receptor–positive BC. Methods As part of a multicenter, prospective cohort of women with a diagnosis of BC at or under the age of 40 years, participants were surveyed 30 months after their diagnosis about adherent behaviors. Among those who reported taking ET, adherence was measured with a 3‐item Likert‐type scale: Do you ever forget to take your ET? If you feel worse when you take your ET, do you stop taking it? Did you take your ET exactly as directed by your doctor over the last 3 months? Women reporting at least 1 nonadherent behavior were classified as nonadherers. Variables with a P value <.20 were included in a multivariable logistic model. Results Among 384 women, 194 (51%) were classified as nonadherers. Univariate factors that retained significance in the multivariable model included educational level (odds ratio [OR], 0.50 for high vs low; P = .04), level of social support according to the Medical Outcome Study Social Support Survey (OR, 0.98 per 1 point; P = .01), and confidence with the decision regarding ET measured on a 0 to 10 numerical scale (OR, 0.63 for high vs low; P = .04). Conclusions Findings from this study could help to identify young patients at higher risk for nonadherence. Interventions adapted to the level of education and aimed at reinforcing support and patients' confidence in their decision to take ET could improve adherence and associated outcomes in this population.
Abstract GS6-06: Local therapy and quality of life outcomes in young women with breast cancer
Dominici, LS, Hu, Jianwen , King, TA, Ruddy, KJ, Tamimi, RM, Peppercorn, J, Schapira, Lidia , Borges, VF, Come, SE, Warner, E , Partridge, AH, Rosenberg, SM

Cancer Research | May 11, 2019 | Volume: 79 | Issue: 4_Supplement | Pages: GS6-06-GS6-06

10.1158/1538-7445.sabcs18-gs6-06 Get It

Abstract Background: Increasing rates of mastectomy, primarily bilateral mastectomy (BMx), have been most dramatic in young women with breast cancer (BC). Impact on long-term quality of life (QOL) is largely unknown. Methods: Between 10/2016-11/2017, we administered the BREAST-Q, a validated patient-reported outcomes measure, to women dx with BC at age ≤40 in a large prospective cohort study. Demographic and treatment information was obtained by surveys and chart review. Mean BREAST-Q scores for each domain (breast satisfaction, physical, psychosocial, and sexual) were compared by surgery types; higher BREAST-Q scores (range: 0-100) indicate better QOL. Linear regression was used to identify predictors of BREAST-Q domain scores. Results: 581 women with stage 0-3 BC completed the BREAST-Q a median of 5.8 years from dx. Median age at dx was 37 (range: 26-40) years; 86% had stage 0, 1 or 2 disease; 28% had breast-conserving surgery (BCS); 72% had mastectomy (Mx), among whom 72% underwent BMx and 89% had reconstruction. Mean BREAST-Q scores (unadjusted) for breast satisfaction, psychosocial, and sexual well-being were lower for patients having unilateral mastectomy (UMx) or BMx compared to BCS; physical function was similar among groups. In multivariate analysis, lower BREAST-Q psychosocial scores were associated with radiation and Mx (UMx or BMx). Lower sexual well-being scores were also associated with Mx. Lower satisfaction with breast scores following radiation were of a clinically significant magnitude (β -8.1 95% CI -11.9- -4.3, p-value 0.03). Lower scores for physical well-being were seen for patients reporting lymphedema and higher for those who had undergone surgery more than 5 years prior. Lower scores across all 4 domains were associated with reported financial distress. BREAST-Q domain mean scores (SD) BMxUMxBCSp-valueBreast satisfaction60.3 (18.9)59.5 (21.3)65.9 (20.7)0.008Physical well-being78.6 (14.9)79.7 (15.1)78.9 (15.5)0.8Psychosocial well-being68.1 (20.8)70.5 (21.2)76.1 (20.5)&lt;0.001Sexual well-being48.6 (21.3)53.2 (21.7)57.5 (18.7)&lt;0.001SD Standard deviation Conclusion: Local therapy in young breast cancer survivors may have a persistent impact on their breast satisfaction, psychosocial, and sexual outcomes, with particular effects from UMx or BMx. Socio-economic stressors also appear to play a role. When counseling young women about their surgical decisions, knowledge of potential long-term QOL impact is of critical importance. Citation Format: Dominici LS, Hu J, King TA, Ruddy KJ, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Partridge AH, Rosenberg SM. Local therapy and quality of life outcomes in young women with breast cancer [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 GS6-06.