Search

Background: Higher circulating carotenoids are associated with lower breast cancer risk. The underlying biology remains under-explored. Methods: We profiled 293 prediagnostic plasma metabolites in a nested case–control study (n = 887 cases) within the Nurses' Health Studies. Associations between circulating carotenoids and metabolites were identified using linear-mixed models (FDR ≤ 0.05), and we further selected metabolites most predictive of carotenoids with LASSO. Metabolic signatures for carotenoids were calculated as weighted sums of LASSO selected metabolites. We further evaluated the metabolic signatures in relation to breast cancer risk using conditional logistic-regression. Results: We identified 48 to 110 metabolites associated with plasma levels of α-carotene, β-carotene, β-cryptoxanthin, estimated-vitamin-A-potential, lutein/zeaxanthin, and lycopene, which included primarily positively associated metabolites implicated in immune regulation (tryptophan), redox balance (plasmalogens, glutamine), epigenetic regulations (acetylated-/methylated-metabolites), and primarily inversely associated metabolites involved in β-oxidation (carnitines; FDR ≤ 0.05). The metabolomic signatures derived for β-carotene (Q4 vs. Q1 relative risk RR = 0.74, Ptrend = 0.02), and estimated-vitamin-A-potential (Q4 vs. Q1 RR = 0.74, Ptrend = 0.02)—measured ≥10 years before diagnosis—were associated with lower breast cancer risk. Modest attenuations of RR for measured levels of β-carotene and estimated-vitamin-A-potential were seen when we adjusted for their corresponding metabolic signatures. Conclusions: Metabolites involved in immune regulation, redox balance, membrane signaling, and β-oxidation were associated with plasma carotenoids. Although some metabolites may reflect shared common food sources or compartmental colocalization with carotenoids, others may signal the underlying pathways of carotenoids-associated lowered breast cancer risk. Impact: Consumption of carotenoid-rich diet is associated with a wide-range of metabolic changes which may help to reduce breast cancer risk.

BACKGROUND: To assess the risk of cardiovascular mortality among cancer survivors who developed breast cancer as a second malignancy (BCa-2) compared with patients with first primary breast cancer (BCa-1) and the general population. METHODS: Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 1,024,047 BCa-1 and 41,744 BCa-2 patients diagnosed from the age 30 between 1975 and 2016, and the corresponding US female population (994,415,911 person-years; 5,403,551 cardiovascular deaths). Compared with the general population and BCa-1 patients, we calculated incidence rate ratios (IRRs) of cardiovascular deaths among BCa-2 patients using Poisson regression. To adjust for unmeasured confounders, we performed a nested, case-crossover analysis among BCa-2 patients who died from cardiovascular disease. RESULTS: Although BCa-2 patients had a mildly increased risk of cardiovascular mortality compared with the population (IRR 1.08) and BCa-1 patients (IRR 1.15), the association was pronounced among individuals aged 30–49 years (BCa-2 vs. population: IRR 6.61; BCa-2 vs. BCa-1: IRR 3.03). The risk elevation was greatest within the first month after diagnosis, compared with the population, but comparable with BCa-1 patients. The case-crossover analysis confirmed these results. CONCLUSION: Our findings suggest that patients with BCa-2 are at increased risk of cardiovascular mortality.

PURPOSE This study assessed the joint association of pathogenic variants (PVs) in breast cancer (BC) predisposition genes and polygenic risk scores (PRS) with BC in the general population. METHODS A total of 26,798 non-Hispanic white BC cases and 26,127 controls from predominately population-based studies in the Cancer Risk Estimates Related to Susceptibility consortium were evaluated for PVs in BRCA1, BRCA2, ATM, CHEK2, PALB2, BARD1, BRIP1, CDH1, and NF1. PRS based on 105 common variants were created using effect estimates from BC genome-wide association studies; the performance of an overall BC PRS and estrogen receptor–specific PRS were evaluated. The odds of BC based on the PVs and PRS were estimated using penalized logistic regression. The results were combined with age-specific incidence rates to estimate 5-year and lifetime absolute risks of BC across percentiles of PRS by PV status and first-degree family history of BC. RESULTS The estimated lifetime risks of BC among general-population noncarriers, based on 10th and 90th percentiles of PRS, were 9.1%-23.9% and 6.7%-18.2% for women with or without first-degree relatives with BC, respectively. Taking PRS into account, more than 95% of BRCA1, BRCA2, and PALB2 carriers had > 20% lifetime risks of BC, whereas, respectively, 52.5% and 69.7% of ATM and CHEK2 carriers without first-degree relatives with BC, and 78.8% and 89.9% of those with a first-degree relative with BC had > 20% risk. CONCLUSION PRS facilitates personalization of BC risk among carriers of PVs in predisposition genes. Incorporating PRS into BC risk estimation may help identify > 30% of CHEK2 and nearly half of ATM carriers below the 20% lifetime risk threshold, suggesting the addition of PRS may prevent overscreening and enable more personalized risk management approaches.

Type II diabetes is associated with poor breast cancer prognosis. To study the association between a diabetes risk reduction diet (DRRD) and survival following breast cancer, we followed 8,482 women with breast cancer from two large cohort studies. Information on diet and other factors was repeatedly measured in validated questionnaires every two to four years. The DRRD includes 9 components: higher intakes of cereal fiber, coffee, nuts, whole fruits and polyunsaturated/saturated fat ratio; and lower glycemic index, trans fat, sugar-sweetened beverages, and red meat. Cumulative average DRRD score was calculated using repeated measures of postdiagnostic diet. Deaths were assessed by family members or via National Death Index. Multivariable-adjusted HRs and 95% confidence intervals (CI) were estimated using Cox proportional hazards models. During a median of 14 years of follow-up since diagnosis, 2,600 deaths occurred among participants, 1,042 of which were due to breast cancer. Women with higher postdiagnostic DRRD score had a 20% lower risk of breast cancer–specific mortality (top vs. bottom quintile HR = 0.80; 95% CI = 0.65–0.97; Ptrend = 0.02) and 34% lower risk of all-cause mortality (HR = 0.66; 95% CI = 0.58–0.76; Ptrend < 0.0001). Compared with women who consistently had lower score (≤median) before and after diagnosis, those whose score improved from low to high had a lower risk of breast cancer–specific mortality (HR = 0.77; 95% CI = 0.62–0.95) and overall mortality (HR = 0.85; 95% CI = 0.74–0.97). These findings demonstrate that greater adherence to DRRD was associated with better survival, suggesting postdiagnosis dietary modification consistent with type II diabetes prevention may be important for breast cancer survivors. Significance: This study suggests that greater adherence to the diabetes risk reduction diet after diagnosis associates with improved survival outcomes among a large number of breast cancer survivors.

Background: Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. Methods: We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values-8 as genome-wide significant, and p-values-5 as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants.Results: None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values5. The strongest evidence was found for rs4674019 (p-value=2.27x10-7), which showed genome-wide significant interaction (p-value=3.8x10-8) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. Conclusions: In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT–breast cancer risk association.

Background Cancer survivors who develop breast cancer as a second malignancy (BCa-2) are common. Yet, little is known about the prognosis of BCa-2 compared to first primary breast cancer (BCa-1). Methods Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 883,881 patients with BCa-1 and 36,313 patients with BCa-2 during 1990–2015. Compared with patients with BCa-1, we calculated hazard ratios (HRs) of breast cancer-specific mortality among patients with BCa-2, using multivariable Cox regression. Results During the follow-up (median 5.5 years), 114,964 and 3829 breast cancer-specific deaths were identified among BCa-1 and BCa-2 patients, respectively. Patients with BCa-2 had more favorable tumor characteristics and received less intensive treatment e.g., surgery and chemo−/radio-therapy, compared to patients with BCa-1. When adjusting for demographic factors, patients with BCa-2 were at similar risk of breast cancer-specific mortality (HR 1.00, 95% CI 0.97–1.03) compared to patients with BCa-1. However, when additionally controlling for tumor characteristics and treatment modes, BCa-2 patients were at an increased risk of breast cancer-specific mortality (HR 1.11, 95% CI 1.08–1.15). The risk elevation was particularly greater when the first malignancy was lung, bladder, ovarian or blood malignancy (HRs 1.16–1.85), or when the first malignancy was treated with chemotherapy and radiotherapy (HR 1.44, 95% CI 1.28–1.63). Conclusions Overall, patients with BCa-2 have worse breast cancer-specific survival, compared with their BCa-1 counterparts, although the risk elevation is mild. High-risk subgroups based on first malignancy’s characteristics may be considered for active clinical management.

The impact of patient demographics and local therapy choice on arm morbidity in young breast cancer patients is understudied despite its importance given the long survivorship period. This study assessed patient-reported arm morbidity in the Young Women’s Breast Cancer Study (YWS), a prospective cohort study. From 2006 to 2016, 1302 women with breast cancer diagnosed at the age of 40 years or younger enrolled in the YWS. The participants regularly complete surveys. The response rates are higher than 86%. Using the Breast Cancer Prevention Trial Checklist, this study examined the prevalence of patient-reported postoperative arm swelling and decreased range of motion (ROM) 1 year after diagnosis, stratified by local therapy strategy, in patients who had surgery for stages 1 to 3 disease. Logistic regression analysis was used to identify risk factors for arm morbidity. Among 888 eligible participants (median age, 37 years), 14% reported arm swelling and 34% reported decreased ROM at 1 year. Arm swelling was reported by 23.6% of the patients who had axillary lymph node dissection (ALND) and 24.6% of the patients who received ALND and post-mastectomy radiation therapy (PMRT). In the multivariable analysis, the patients who reported being financially uncomfortable or who had ALND were at higher risk of arm swelling at 1 year. Being overweight, receiving ALND after sentinel lymph node biopsy, and receiving PMRT were associated with decreased ROM at 1 year. High rates of self-reported arm morbidity in young breast cancer survivors were reported, particularly in patients receiving ALND and PMRT. Attention to the risks and benefits of differing local therapy strategies for ALND and PMRT patients is warranted.

Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype. Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer–specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype. Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype (Padj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5–25 kg/m2 [HR (95% confidence interval (CI), 1.19 (1.06–1.34)]; current versus never smoking [1.37 (1.27–1.47)], high versus low physical activity [0.43 (0.21–0.86)], age ≥30 years versus 0– Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype. Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care.

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 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.

Background: Reproductive factors related to childbearing are recognized as breast cancer risk factors. Whether any of these factors could influence adult breast tissue composition is unclear. We investigated the associations of reproductive factors with percentage of epithelium, stroma, and fat tissue in benign breast biopsy samples. Methods: This study included 983 cancer-free women with biopsy-confirmed benign breast disease (BBD) within the Nurses’ Health Study and Nurses’ Health Study II cohorts. Percentage of each tissue type (epithelium stroma, and fat) was measured on whole section images with a deep-learning technique. All tissue measures were log-transformed in all the analyses to improve normality. The data on reproductive variables and other breast cancer risk factors were obtained from biennial questionnaires. Generalized linear regression was used to examine the associations of reproductive factors (parity, age at first birth, breastfeeding, age at menarche and the duration of the interval between menarche and age at first birth) with percentage of tissue types, while adjusting for known breast cancer risk factors.Results: In this study of 983 cancer-free women, 299 (30.4%) had non-proliferative disease, 559 (56.9%) had proliferative disease without atypia, and 125 (12.7%) had atypical hyperplasia, consistent with previously reported distributions of these BBD subtypes. The average proportion of epithelium, stroma, and fat in our study sample was 9.1% (range 0.5-52.2%), 72.4% (range 23.6-99.0%), and 18.5% (range 0-71.3%), respectively. As compared to parous women, nulliparous women had a smaller percentage of epithelium (β= -0.26, 95% confidence interval [CI] -0.41, -0.11) and fat (β= -0.34, 95% CI -0.54, -0.13) and a greater percentage of stroma (β=0.04, 95% CI 0.01, 0.08). Among parous women, number of children was inversely associated with percentage of stroma (β per child= -0.01 (-0.02, -0.00). Duration of breastfeeding of ≥24 months was associated with a reduced proportion of fat (β= -0.30, 95% CI -0.54, -0.06; p-trend=0.04). In a separate analysis restricted to premenopausal women, being nulliparous was associated with a greater proportion of stroma (β=0.06, 95% CI 0.02, 0.10) and smaller proportion of epithelium (β= -0.22, 95% CI -0.38, -0.06) and fat (β= -0.32, 95% CI -0.56, -0.08). Greater parity and older age at first birth were both associated with a greater proportion of epithelium (and a smaller proportion of stroma. The age at menarche and the duration of the interval between age at menarche and first birth were not associated with the proportion of any of the tissue types. Conclusions: Our findings suggest that reproductive factors with a protective effect on breast cancer risk may be associated with a greater proportion of epithelium and a smaller proportion of stroma, potentially suggesting importance of epithelial-stromal interactions. Future studies are warranted to confirm our findings and to elucidate the underlying biological mechanisms. Citation Format: Lusine Yaghjyan, Rebecca J Austin-Datta, Hannah Oh, Yujing J Heng, Adithya D Vellal, Korsuk Sirinukunwattana, Gabrielle M Baker, Laura Collins, Divya Murthy, Bernard Rosner, Rulla M Tamimi. Reproductive breast cancer risk factors and breast tissue composition on benign breast biopsies [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 PS7-90.

Importance: Type 2 diabetes (T2D) is associated with poor breast cancer prognosis. Adherence to a dietary pattern associated with lower T2D risk may improve breast cancer outcomes. Objective: To evaluate the association between adherence to a diabetes risk reduction diet (DRRD) after diagnosis and survival outcomes following breast cancer. Method: We followed 8,320 women diagnosed with stage I-III breast cancer from two large prospective cohort studies, the Nurses’ Health Study (NHS; 1980-2014) and the NHSII (1991-2015). Information on diet and other covariates was repeatedly measured in validated follow-up questionnaires every two to four years. The DRRD adherence score includes 9 dietary components: higher intakes of cereal fiber, coffee, nuts, whole fruits and polyunsaturated:saturated fat ratio; and lower glycemic index of diet, lower intakes of trans fat, sugar-sweetened beverages/fruit juices, and red meat. Cumulative average DRRD score was calculated using repeated measures of diet after breast cancer diagnosis. Deaths were reported by family members or via the search of National Death Index, and cause of death was assigned by reviewing death certificates/medical records. Multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between DRRD score and breast cancer-specific and all-cause mortality were estimated using Cox proportional hazards models. Results: During a median of 16 years of follow-up after diagnosis, we ascertained 2,146 deaths, of which 948 were due to breast cancer. In the multivariable-adjusted models, women with higher post-diagnostic DRRD scores had a 17% lower risk of breast cancer-specific mortality (top vs. bottom quintile HR =0.83; 95%CI=0.67-1.02; p-trend=0.03) and 33% lower risk of all-cause mortality (HR =0.67; 95%CI=0.58-0.78; p-trend Conclusion: We found that greater adherence to the DRRD after breast cancer diagnosis was associated with better survival, suggesting dietary modification after diagnosis consistent with T2D prevention may be important to breast cancer survivors. Table 1. Multivariable HRs and 95% CIs for the association between post-diagnostic diabetes risk reduction diet score and mortality among breast cancer survivors using pooled data from NHS abd NHSII (N=8,320)Quintile 1Quintile 2Quintile 3Quintile 4Quintile 5p-trendMedian (IQR)20 (18-21)24 (23-25)27 (26-28)30 (29-31)34 (33-37)Breast cancer-specific mortalityNo. of events (n=948), 589,953 py207205184176176Model 11 (referent)0.97 (0.80-1.18)0.80 (0.65-0.97)0.79 (0.64-0.96)0.75 (0.61-0.92)0.0008Model 21 (referent)0.88 (0.72-1.07)0.76 (0.62-0.93)0.77 (0.63-0.95)0.83 (0.67-1.02)0.03Model 31 (referent)0.99 (0.81-1.20)0.82 (0.67-1.00)0.85 (0.69-1.04)0.86 (0.70-1.07)0.06All-cause mortalityNo. of events (n=2,146), 589,953 py506447476383334Model 11 (referent)0.83 (0.73-0.94)0.80 (0.71-0.91)0.67 (0.59-0.76)0.57 (0.50-0.65) Table 2. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between changes of diabetes risk reduction diet score before or after diagnosis and mortality among breast cancer survivors using pooled data from NHS abd NHSII (N=8,320)CharacteristicsHR (95% CI)Breast cancer-specific mortalityCross classified changesNo. of events (n=948), 589,953 pyLow to Low1 (referent)Low to High0.81 (0.65-1.00)High to Low0.97 (0.79-1.19)High to High0.87 (0.74-1.02)All-cause mortalityCross classified changesNo. of events (n=2,306), 589,953 pyLow to Low1 (referent)Low to High0.88 (0.76-1.02)High to Low0.99 (0.87-1.12)High to High0.80 (0.72-0.89) Citation Format: Tengteng Wang, Maryam Farvid, Jae Hee Kang, Michelle Holmes, Bernard Rosner, Rulla Tamimi, Walter Willett, A. Heather Eliassen. Diabetes risk reduction diet and survival following 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 GS2-09.

BACKGROUND: Population-based estimates of the risk of breast cancer associated with germline pathogenic variants in cancer-predisposition genes are critically needed for risk assessment and management in women with inherited pathogenic variants. METHODS: In a population-based case–control study, we performed sequencing using a custom multigene amplicon-based panel to identify germline pathogenic variants in 28 cancer-predisposition genes among 32,247 women with breast cancer (case patients) and 32,544 unaffected women (controls) from population-based studies in the Cancer Risk Estimates Related to Susceptibility (CARRIERS) consortium. Associations between pathogenic variants in each gene and the risk of breast cancer were assessed. RESULTS: Pathogenic variants in 12 established breast cancer–predisposition genes were detected in 5.03% of case patients and in 1.63% of controls. Pathogenic variants in BRCA1 and BRCA2 were associated with a high risk of breast cancer, with odds ratios of 7.62 (95% confidence interval [CI], 5.33 to 11.27) and 5.23 (95% CI, 4.09 to 6.77), respectively. Pathogenic variants in PALB2 were associated with a moderate risk (odds ratio, 3.83; 95% CI, 2.68 to 5.63). Pathogenic variants in BARD1, RAD51C, and RAD51D were associated with increased risks of estrogen receptor–negative breast cancer and triple-negative breast cancer, whereas pathogenic variants in ATM, CDH1, and CHEK2 were associated with an increased risk of estrogen receptor–positive breast cancer. Pathogenic variants in 16 candidate breast cancer–predisposition genes, including the c.657_661del5 founder pathogenic variant in NBN, were not associated with an increased risk of breast cancer. CONCLUSIONS: This study provides estimates of the prevalence and risk of breast cancer associated with pathogenic variants in known breast cancer–predisposition genes in the U.S. population. These estimates can inform cancer testing and screening and improve clinical management strategies for women in the general population with inherited pathogenic variants in these genes. (Funded by the National Institutes of Health and the Breast Cancer Research Foundation.)

Background: We investigated the associations of postdiagnostic dietary glycemic index (GI), glycemic load (GL), insulin index (II), and insulin load (IL) with breast cancer–specific and all-cause mortality. Methods: Among 8,932 women with stage I–III breast cancer identified in the Nurses' Health Study (NHS; 1980–2010) and NHSII (1991–2011), we prospectively evaluated the associations between postdiagnostic GI, GL, II, and IL, and breast cancer–specific and all-cause mortality. Participants completed a validated food frequency questionnaire every 4 years after diagnosis. Results: During follow-up by 2014 in the NHS and 2015 in the NHSII, 2,523 deaths, including 1,071 from breast cancer, were documented. Higher postdiagnostic GL was associated with higher risk of both breast cancer–specific mortality [HRQ5vsQ1 = 1.33; 95% confidence interval (CI) = 1.09–1.63; Ptrend = 0.008] and all-cause mortality (HRQ5vsQ1 = 1.26; 95% CI = 1.10–1.45; Ptrend = 0.0006). Higher all-cause mortality was also observed with higher postdiagnostic GI (HRQ5vsQ1 = 1.23; 95% CI = 1.08–1.40; Ptrend = 0.001), II (HRQ5vsQ1 = 1.20; 95% CI = 1.04–1.38; Ptrend = 0.005), and IL (HRQ5vsQ1 = 1.23; 95% CI = 1.07–1.42; Ptrend = 0.0003). The associations were not modified by insulin receptor or estrogen receptor status of the tumor, or body mass index. Conclusions: We found that higher dietary GL, reflecting postprandial glucose response, after a breast cancer diagnosis was associated with higher risk of breast cancer–specific mortality. Higher dietary GI, GL, II, and IL after a breast cancer diagnosis were associated with higher risk of death from any cause. Impact: These results suggest that carbohydrate quantity and quality may be important in breast cancer prognosis. See related commentary by McTiernan, p. 252

OBJECTIVE This study aimed to uncover genetic contributors to adiposity in early life. METHODS A genome-wide association study of childhood body fatness in 34,401 individuals within the Nurses' Health Studies and the Health Professionals Follow-up Study was conducted. Data were imputed to the 1000 Genomes Phase 3 version 5 reference panel. RESULTS A total of 1,354 single-nucleotide polymorphisms (P

We evaluated the association of percent mammographic density (PMD), absolute dense area (DA), and non-dense area (NDA) with risk of “intrinsic” molecular breast cancer (BC) subtypes. We pooled 3492 invasive BC and 10,148 controls across six studies with density measures from prediagnostic, digitized film-screen mammograms. We classified BC tumors into subtypes [63% Luminal A, 21% Luminal B, 5% HER2 expressing, and 11% as triple negative (TN)] using information on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. We used polytomous logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CI) for density measures (per SD) across the subtypes compared to controls, adjusting for age, body mass index and study, and examined differences by age group. All density measures were similarly associated with BC risk across subtypes. Significant interaction of PMD by age (P = 0.001) was observed for Luminal A tumors, with stronger effect sizes seen for younger women

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 NAC influences surgical decisions in young women. METHODS The Young Women's Breast Cancer Study (YWS), 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 (cCR and pCR), 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), cCR (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 choose mastectomy, suggesting that surgical decisions are often driven by factors beyond extent of disease and treatment response.

Synchronous bilateral breast cancer is uncommon, and its pattern and incidence among younger women is unknown. Here we report the incidence, phenotypes, and long-term oncologic outcomes of bilateral breast cancer in women enrolled in the Young Women’s Breast Cancer Study (YWS). The YWS is a multi-center, prospective cohort study of women with breast cancer diagnosed at age ≤ 40 years. Those with synchronous bilateral breast cancer formed our study cohort. Tumor phenotypes were categorized as luminal A (hormone receptor (HR)+/HER2−/grade 1/2), luminal B (HR+ /HER2+ or HER2− and grade 3), HER2-enriched (HR−/HER2+), or basal-like (HR−/HER2−). Descriptive statistics were used to evaluate tumor phenotypes of bilateral cancers for concordance. Among 1302 patients enrolled in the YWS, 21 (1.6%) patients had synchronous bilateral disease. The median age of diagnosis was 38 years (range 18–40 years). Seventeen (81.0%) underwent genetic testing with 6 found to have pathogenic germline mutations in BRCA1, BRCA2, or TP53. The majority of patients (76.2%) underwent bilateral mastectomy. On pathology, 2 patients had bilateral in-situ disease, 6 had unilateral invasive and contralateral in-situ disease, and 13 had bilateral invasive disease. Of those with bilateral invasive disease, 10 (76.9%) had bilateral luminal tumors and, when fully characterized, 6 were of the same luminal subtype. Only 1 patient had bilateral basal-like breast cancer. At median follow-up of 8.2 years, 14 patients are alive with no recurrent disease. Bilateral breast cancer is uncommon among young women diagnosed with breast cancer at age ≤ 40. In our cohort, the majority of invasive tumors were of the luminal phenotype, though some differed by grade or HER2 status. These findings support the need for thorough pathologic workup of bilateral disease when it is found in young women with breast cancer to determine risk and tailor treatment.

The 21-gene Breast Recurrence Score test predicts benefit from adjuvant chemotherapy in estrogen receptor-positive, HER2-negative (ER+/HER2−) breast cancer (BC). We examined whether the 21-gene assay predicts response to neoadjuvant chemotherapy (NCT). We identified patients with stage I–III ER+/HER2− BC treated with NCT from the Young Women’s Breast Cancer Study, a prospective cohort of women diagnosed with BC at age ≤40 years. The 21-gene assay was performed on tumor specimens removed prior to NCT either as part of clinical care or retrospectively for research. Pathological complete response (pCR) was defined as ypT0/is ypN0. The relationship between Recurrence Score result and pCR was evaluated using logistic regression modeling. 76 women received NCT for ER+/HER2− BC and were eligible for this analysis. Median age at diagnosis was 37 years (range 24–40). Scores ranged between 5 and 77 with 50% >25 and 5% 25 was 21% (8/38) vs. 5% in patients with scores

Immunohistochemical (IHC) staining in breast cancer shows both gain and loss of COX2 expression with disease risk and progression. We investigated four common COX2 antibody clones and found high specificity for purified human COX2 for three clones; however, recognition of COX2 in cell lysates was clone dependent. Biochemical characterization revealed two distinct forms of COX2, with SP21 recognizing an S-nitrosylated form, and CX229 and CX294 recognizing non-nitrosylated COX2 antigen. We found S-nitrosylated and non-nitrosylated COX2 occupy different subcellular locations in normal and breast cancer tissue, implicating distinct synthetic/trafficking pathways and function. Dual stains of ~2000 breast cancer cases show early-onset breast cancer had increased expression of both forms of COX2 compared to postmenopausal cases. Our results highlight the strengths of using multiple, highly characterized antibody clones for COX2 IHC studies and raise the prospect that S-nitrosylation of COX2 may play a role in breast cancer biology.

Objective:Evaluate associations between orange juice (OJ) consumption and anthropometric parameters.Design:Prospective cohort study assessing the association between OJ intake and changes in BMI and height-for-ageZ-score (HAZ) using mixed linear regression.Setting:2004–2008, USA.Participants:Children from the Growing Up Today Study II (n7301), aged 9–16 years at enrollment.Results:OJ consumption was positively associated with 2-year change in HAZ in girls (mean (se)): 0·03 (0·01) for non-consumers, 0·03 (0·02) for 1–3 glasses/month, 0·06 (0·01) for 1–6 glasses/week and 0·09 (0·02) for ≥1 glass/d after full adjustment (Ptrend= 0·02). However, OJ consumption was not associated with 2-year change in BMI percentile (kg/m2, mean (se)): –0·44 (0·36) for non-consumers, 0·20 (0·41) for 1–3 glasses/month, –0·04 (0·34) for 1–6 glasses/week and –0·77 (0·62) for ≥1 glass/d in girls,Ptrend= 0·81; –0·94 (0·53) for non-consumers, –1·68 (0·52) for 1–3 glasses/month, –0·81 (0·38) for 1–6 glasses per week and –1·12 (0·61) for ≥1 glass/d in boys,Ptrend= 0·49.Conclusion:OJ consumption was favourably associated with height growth but unrelated to excess weight gain. OJ may be a useful alternative to whole fruit in the event that whole fruit intake is insufficient.

To examine associations of healthy lifestyle during pregnancy with body mass index (BMI) and risk of overweight or obesity of grandchildren during adolescence and young adulthood. Our study population included 14,001 grandmother–mother–child triads comprised of participants of two ongoing prospective cohort studies of related individuals. We used self-reported grand-maternal gestational weight gain, diet, physical activity, and smoking during pregnancy to create a lifestyle score ranged from 0 to 12, with a higher score indicating healthier lifestyle. Grandchild BMI was self-assessed in follow-up questionnaires. Compared with individuals whose grandmothers had the least healthy lifestyle during pregnancy, individuals whose grandmothers had the most healthy lifestyle had 0.17 (95% CI 0.01, 0.33; P for trend = 0.05) kg/m2 lower BMI and 7% (95% CI 2%, 12%; P for trend = 0.001) lower risk of overweight or obesity during adolescence and young adulthood. The inverse associations between grand-maternal lifestyle and BMI in grandchildren were mainly mediated by maternal pre-pregnancy BMI (mediation effect: 64%; P value = 0.001). Overall, maternal BMI, along with maternal socioeconomic status and lifestyle factors in the second and third generations accounted for all of the inter-generational association (mediation effect: 99%; P value

Summary Background Data on patients with COVID-19 who have cancer are lacking. Here we characterise the outcomes of a cohort of patients with cancer and COVID-19 and identify potential prognostic factors for mortality and severe illness. Methods In this cohort study, we collected de-identified data on patients with active or previous malignancy, aged 18 years and older, with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from the USA, Canada, and Spain from the COVID-19 and Cancer Consortium (CCC19) database for whom baseline data were added between March 17 and April 16, 2020. We collected data on baseline clinical conditions, medications, cancer diagnosis and treatment, and COVID-19 disease course. The primary endpoint was all-cause mortality within 30 days of diagnosis of COVID-19. We assessed the association between the outcome and potential prognostic variables using logistic regression analyses, partially adjusted for age, sex, smoking status, and obesity. This study is registered with ClinicalTrials.gov, NCT04354701, and is ongoing. Findings Of 1035 records entered into the CCC19 database during the study period, 928 patients met inclusion criteria for our analysis. Median age was 66 years (IQR 57–76), 279 (30%) were aged 75 years or older, and 468 (50%) patients were male. The most prevalent malignancies were breast (191 [21%]) and prostate (152 [16%]). 366 (39%) patients were on active anticancer treatment, and 396 (43%) had active (measurable) cancer. At analysis (May 7, 2020), 121 (13%) patients had died. In logistic regression analysis, independent factors associated with increased 30-day mortality, after partial adjustment, were: increased age (per 10 years; partially adjusted odds ratio 1·84, 95% CI 1·53–2·21), male sex (1·63, 1·07–2·48), smoking status (former smoker vs never smoked: 1·60, 1·03–2·47), number of comorbidities (two vs none: 4·50, 1·33–15·28), Eastern Cooperative Oncology Group performance status of 2 or higher (status of 2 vs 0 or 1: 3·89, 2·11–7·18), active cancer (progressing vs remission: 5·20, 2·77–9·77), and receipt of azithromycin plus hydroxychloroquine (vs treatment with neither: 2·93, 1·79–4·79; confounding by indication cannot be excluded). Compared with residence in the US-Northeast, residence in Canada (0·24, 0·07–0·84) or the US-Midwest (0·50, 0·28–0·90) were associated with decreased 30-day all-cause mortality. Race and ethnicity, obesity status, cancer type, type of anticancer therapy, and recent surgery were not associated with mortality. Interpretation Among patients with cancer and COVID-19, 30-day all-cause mortality was high and associated with general risk factors and risk factors unique to patients with cancer. Longer follow-up is needed to better understand the effect of COVID-19 on outcomes in patients with cancer, including the ability to continue specific cancer treatments. Funding American Cancer Society, National Institutes of Health, and Hope Foundation for Cancer Research.

Background: Emerging evidence supports a role of the receptor activator of NF-κB (RANK) pathway in normal mammary gland development and breast carcinogenesis. Osteoprotegerin (OPG) is the endogenous decoy receptor for RANK-ligand (RANKL), which inhibits RANK-signaling. Whether OPG may be a biomarker of breast cancer risk remains unclear. Methods: We evaluated the association between plasma OPG and breast cancer risk in a case (n = 297)–control (n = 297) study nested within the Nurses' Health Study II. Cases were women who were cancer-free and premenopausal at blood collection who developed invasive breast cancer. OPG was quantified using an ELISA. Conditional logistic regression was used to estimate multivariable odds ratios (OR) and 95% confidence intervals (CI) for the association between OPG levels and breast cancer risk, adjusting for potential confounders. Unconditional logistic regression, additionally adjusting for matching factors, was used for stratified analyses. Results: Overall, there was no substantial evidence for an association between plasma OPG levels and breast cancer risk, although the point estimate for the highest (vs. lowest) quartile was below 1 (OR = 0.78; 95% CI, 0.46–1.33; Ptrend = 0.30). There was no evidence of heterogeneity by various reproductive, hormonal, or tumor characteristics, including hormone receptor status and grade (all Pheterogeneity ≥ 0.17). Conclusions: Findings from this prospective study do not provide substantial evidence for an association between circulating OPG and breast cancer risk among premenopausal women; however, we were underpowered in stratified analyses. Impact: Results do not provide strong evidence for OPG as a potential biomarker of breast cancer risk among premenopausal women.

PURPOSE: We investigated the associations of aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) with mammographic breast density (MBD) and their interactions in relation to breast cancer risk. METHODS: This study included 3,675 cancer-free women within the Nurses’ Health Study (NHS) and Nurses’ Health Study II (NHSII) cohorts. Percent breast density (PD), absolute dense area (DA), and non-dense area (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square root-transformed. Information on medication use was collected in 1980 (NHS) and 1989 (NHSII) and updated biennially. Medication use was defined as none, past or current; average cumulative dose and frequency were calculated for all past or current users from all bi-annual questionnaires preceding the mammogram date. We used generalized linear regression to quantify associations of medications with MBD. Two-way interactions were examined in logistic regression models. RESULTS: In multivariate analysis, none of the anti-inflammatory medications were associated with PD, DA and NDA. We found no interactions of any of the medications with PD with respect to breast cancer risk (all p-interactions>0.05). However, some of the aspirin variables appeared to have positive associations with breast cancer risk limited only to women with PD 10–24% (past aspirin OR=1.56, 95% CI 1.03–2.35; current aspirin with

Adherence to healthful dietary patterns is associated with lower body mass index (BMI) in adults; however, whether maternal diet quality during peripregnancy is related to a lower overweight risk in the offspring remains to be elucidated. We investigated the associations between the Alternate Healthy Eating Index (AHEI), Alternate Mediterranean Diet (aMED) and Dietary Approach to Stop Hypertension (DASH) during peripregnancy and offspring weight outcomes in a study including 2729 mother–child pairs from the Nurses’ Health Study II and offspring cohort Growing Up Today Study II. Children, 12–14 years at baseline were 21–23 years at the last follow-up. Overweight or obesity was defined according to International Obesity Task Force (

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 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.

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 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 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.

Background: The V measure captures grayscale intensity variation on a mammogram and is positively associated with breast cancer risk, independent of percent mammographic density (PMD), an established marker of breast cancer risk. We examined whether anthropometrics are associated with V, independent of PMD. Methods: The analysis included 1,700 premenopausal and 1,947 postmenopausal women without breast cancer within the Nurses' Health Study (NHS) and NHSII. Participants recalled their body fatness at ages 5, 10, and 20 years using a 9-level pictogram (level 1: most lean) and reported weight at age 18 years, current adult weight, and adult height. V was estimated by calculating standard deviation of pixels on screening mammograms. Linear mixed models were used to estimate beta coefficients (ß) and 95% confidence intervals (CI) for the relationships between anthropometric measures and V, adjusting for confounders and PMD. Results: V and PMD were positively correlated (Spearman r = 0.60). Higher average body fatness at ages 5 to 10 years (level ≥ 4.5 vs. 1) was significantly associated with lower V in premenopausal (ß = −0.32; 95% CI, −0.48 to −0.16) and postmenopausal (ß = −0.24; 95% CI, −0.37 to −0.10) women, independent of current body mass index (BMI) and PMD. Similar inverse associations were observed with average body fatness at ages 10 to 20 years and BMI at age 18 years. Current BMI was inversely associated with V, but the associations were largely attenuated after adjustment for PMD. Height was not associated with V. Conclusions: Our data suggest that early-life body fatness may reflect lifelong impact on breast tissue architecture beyond breast density. However, further studies are needed to confirm the results. Impact: This study highlights strong inverse associations of early-life adiposity with mammographic image intensity variation.

Genome-wide analysis identifies 32 loci associated with breast cancer susceptibility, accounting for estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. Breast cancer susceptibility variants frequently show heterogeneity in associations by tumor subtype(1-3). To identify novel loci, we performed a genome-wide association study including 133,384 breast cancer cases and 113,789 controls, plus 18,908 BRCA1 mutation carriers (9,414 with breast cancer) of European ancestry, using both standard and novel methodologies that account for underlying tumor heterogeneity by estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 status and tumor grade. We identified 32 novel susceptibility loci (P < 5.0 x 10(-8)), 15 of which showed evidence for associations with at least one tumor feature (false discovery rate < 0.05). Five loci showed associations (P < 0.05) in opposite directions between luminal and non-luminal subtypes. In silico analyses showed that these five loci contained cell-specific enhancers that differed between normal luminal and basal mammary cells. The genetic correlations between five intrinsic-like subtypes ranged from 0.35 to 0.80. The proportion of genome-wide chip heritability explained by all known susceptibility loci was 54.2% for luminal A-like disease and 37.6% for triple-negative disease. The odds ratios of polygenic risk scores, which included 330 variants, for the highest 1% of quantiles compared with middle quantiles were 5.63 and 3.02 for luminal A-like and triple-negative disease, respectively. These findings provide an improved understanding of genetic predisposition to breast cancer subtypes and will inform the development of subtype-specific polygenic risk scores.

Background Breast cancer in young women is more likely to have higher risk features and be associated with germline BRCA1/BRCA2 mutations. We present the clinicopathologic features of breast cancers in a prospective cohort of young women, and associations between surrogate molecular subtype and BRCA1/BRCA2 mutation status. Methods Histopathological features, biomarker status, tumour stage and BRCA status were collected. Invasive tumours were categorised as luminal A-like (ER + and/or PR + , HER2-, grade 1/2), luminal B-like (ER + and/or PR + , HER2 + , or ER + and/or PR + , HER2-, and grade 3), HER2-enriched (ER/PR-, HER2 + ) or triple-negative. Results In all, 57.3% (654/1143) of invasive tumours were high grade. In total, 32.9% were luminal A-like, 42.4% luminal B-like, 8.3% HER2-enriched, and 16.4% triple-negative. Among different age groups, there were no differences in molecular phenotype, stage, grade or histopathology. 11% (131) of tumours were from BRCA mutation carriers; 64.1% BRCA1 (63.1% triple-negative), and 35.9% BRCA2 (55.3% luminal B-like). Discussion The opportunity to provide comparisons across young age groups, BRCA mutation status, surrogate molecular phenotype, and the identification of more aggressive hormone receptor-positive phenotypes in this population provides direction for future work to further understand and improve disparate outcomes for young women with luminal B-like cancers, particularly BRCA2-associated cancers, with potential implications for tailored prevention and treatment.

Background Excess body weight is an established cause of postmenopausal breast cancer, but it is unknown if weight loss reduces risk. Methods Associations between weight change and risk of breast cancer were examined among women aged 50 years and older in the Pooling Project of Prospective Studies of Diet and Cancer. In 10 cohorts, weight assessed on three surveys was used to examine weight change patterns over approximately 10 years (interval 1 median = 5.2 years; interval 2 median = 4.0 years). Sustained weight loss was defined as no less than 2 kg lost in interval 1 that was not regained in interval 2. Among 180 885 women, 6930 invasive breast cancers were identified during follow-up. Results Compared with women with stable weight (±2 kg), women with sustained weight loss had a lower risk of breast cancer. This risk reduction was linear and specific to women not using postmenopausal hormones (>2–4.5 kg lost: hazard ratio [HR] = 0.82, 95% confidence interval [CI] = 0.70 to 0.96; >4.5– Conclusions These results suggest that sustained weight loss, even modest amounts, is associated with lower breast cancer risk for women aged 50 years and older. Breast cancer prevention may be a strong weight-loss motivator for the two-thirds of American women who are overweight or obese.

Background: We investigated the associations of oral contraceptives (OC) with percent breast density (PD), absolute dense area (DA), nondense area (NDA), and a novel image intensity variation (V) measure in premenopausal women. Methods: This study included 1,233 controls from a nested case–control study within Nurses' Health Study II cohort. Information on OCs was collected in 1989 and updated biennially. OC use was defined from the questionnaire closest to the mammogram date. PD, DA, and NDA were measured from digitized film mammograms using a computer-assisted thresholding technique; the V measure was obtained with a previously developed algorithm measuring the SD of pixel values in the eroded breast region. Generalized linear regression was used to assess associations between OCs and density measures (square root–transformed PD, DA, and NDA, and –untransformed V). Results: OC use was not associated with PD [current vs. never: β = −0.06; 95% confidence interval (CI), −0.37–0.24; past vs. never: β = 0.10; 95% CI, −0.09–0.29], DA (current vs. never: β = −0.20; 95% CI −0.59–0.18; past vs. never: β = 0.13; 95% CI, −0.12–0.39), and NDA (current vs. never: β = −0.19; 95% CI, −0.56–0.18; past vs. never: β = −0.01; 95% CI, −0.28–0.25). Women with younger age at initiation had significantly greater V-measure ( Conclusions: Our findings suggest that an earlier age at first OC use was associated with significantly greater V. Impact: These findings could guide decisions about the age for OC initiation.

Background Fear of cancer recurrence (FCR) is more intense in younger women. Because FCR is a powerful determinant of quality of life, identifying those at risk for persistently elevated FCR can inform timing of interventions. Methods A total of 965 women with stage 0 to stage III breast cancer enrolled in the Young Women's Breast Cancer Study, a prospective cohort of women diagnosed with breast cancer at age ≤40 years, completed the 3-item Lasry Fear of Recurrence Index. Group-based trajectory modeling was used to classify distinct FCR patterns from baseline through 5 years post-diagnosis. Multinomial logistic regression was used to identify patient, disease, and treatment characteristics associated with each trajectory. Results Five FCR trajectories were identified with the majority of participants having moderate (33.1%) or high FCR (27.6%) that improved over time. A total of 6.9% participants had moderate FCR that worsened, whereas 21.7% had high FCR at baseline that remained high throughout. In the fully adjusted multinomial model, stages II and III (vs stage I) were associated with higher odds of being in the high/stable trajectory, whereas stage 0 (vs stage I), being financially comfortable (vs. not comfortable), and White (vs non-White) were associated with higher odds of being in a trajectory that improved over time. Conclusions Although FCR improves over time for many young women with breast cancer, approximately one-third had FCR that was severe and did not improve or worsened over 5 years after diagnosis. Ongoing monitoring is warranted, with early referral to mental health professionals indicated for those at highest risk for unresolved FCR. Lay summary Fear of recurrence is common among young women with breast cancer. The authors followed a large cohort of young women diagnosed with breast cancer when they were 40 years of age and younger, and found 5 distinct trajectories that show moderate and severe fears do not always improve over time and may require targeted mental health intervention.

Young women with breast cancer experience unique treatment and survivorship issues centering on treatment-related amenorrhea (TRA), including fertility preservation and management of ovarian function as endocrine therapy. The Young Women’s Breast Cancer Study (YWS) is a multi-center, prospective cohort study of women diagnosed at age ≤40, enrolled from 2006 to 2016. Menstrual outcomes were self-reported on serial surveys. We evaluated factors associated with TRA using logistic regression. One year post-diagnosis, 286/789 (36.2%) experienced TRA, yet most resumed menses (2-year TRA: 120/699; 17.2%). Features associated with 1-year TRA included older age (OR≤30vs36-40 = 0.29 (0.17–0.48), OR31-35vs36-40 = 0.67 (0.46–0.94), p = 0.02); normal body mass index (BMI) (OR≥25vs18.5-24. =0.59 (0.41–0.83), p chemo vs no chemo = 5.55 (3.60–8.82), p p = 0.01). TRA rates were similar across most standard regimens (docetaxel/carboplatin/trastuzumab +/− pertuzumab: 55.6%; docetaxel/cyclophosphamide +/− trastuzumab/pertuzumab: 41.8%; doxorubicin/cyclophosphamide/paclitaxel +/− trastuzumab/pertuzumab: 44.1%; but numerically lower with AC alone (25%) or paclitaxel/trastuzumab (11.1%). Among young women with breast cancer, lower BMI appears to be an independent predictor of TRA. This finding has important implications for interpretation of prior studies, future research, and patient care in our increasingly obese population. Additionally, these data describe TRA associated with use of docetaxel/cyclophosphamide, which is increasingly being used in lieu of anthracycline-containing regimens. Collectively, these data can be used to inform use of fertility preservation strategies for women who need to undergo treatment as well as the potential need for ovarian suppression following modern chemotherapy for young women with estrogen-receptor-positive breast cancer.Clinical trial registration: www.clinicaltrials.gov, NCT01468246.

BackgroundCopy number variants (CNVs) are pervasive in the human genome but potential disease associations with rare CNVs have not been comprehensively assessed in large datasets. We analysed rare CNVs in genes and non-coding regions for 86,788 breast cancer cases and 76,122 controls of European ancestry with genome-wide array data.ResultsGene burden tests detected the strongest association for deletions in BRCA1 (P= 3.7E-18). Nine other genes were associated with a p-value < 0.01 including known susceptibility genes CHEK2 (P= 0.0008), ATM (P= 0.002) and BRCA2 (P= 0.008). Outside the known genes we detected associations with p-values < 0.001 for either overall or subtype-specific breast cancer at nine deletion regions and four duplication regions. Three of the deletion regions were in established common susceptibility loci.ConclusionsThis is the first genome-wide analysis of rare CNVs in a large breast cancer case-control dataset. We detected associations with exonic deletions in established breast cancer susceptibility genes. We also detected suggestive associations with non-coding CNVs in known and novel loci with large effects sizes. Larger sample sizes will be required to reach robust levels of statistical significance.

Background: Benign breast disease (BBD) is a term that encompasses a heterogeneous group of lesions with different levels of subsequent breast cancer risk. Large, epidemiologic follow-up studies have consistently shown that proliferative lesions without atypia are associated with a 1.5-2-fold increase in risk whereas atypical hyperplasias are associated with a 4-5-fold increase in risk. However, these data were derived primarily from populations of women who, for the most part, were biopsied before the widespread use of screening mammography and in whom these lesions were incidental findings. Whether or not similar levels of subsequent breast cancer risk are found when these lesions are detected in mammographically screened populations has not been previously investigated. Methods: To address this issue, we performed a nested case-control study within the Nurses’ Health Study (NHS) and NHSII BBD cohorts, including 488 women who had biopsy-proven BBD and on average 9 years later developed breast cancer (cases) and 1,908 women who had biopsy-proven BBD and did not develop breast cancer (controls). We performed logistic regression, adjusting for matching factors and potential confounders, to estimate odds ratios (OR) and 95% confidence intervals (CI) for developing subsequent breast cancer by BBD subtype. We stratified the analyses by the calendar time of BBD diagnosis (pre- vs. post-mammographic era [before vs. after 1985]) and the method of BBD detection (mammogram vs. self-exam/physician’s exam). Interaction tests were performed using the Wald test for product terms. Results: During the pre-mammographic era, proliferative lesions without atypia were associated with a 1.78-fold higher risk of breast cancer (95% CI=1.31-2.42) and atypical hyperplasia was associated with a 4.61-fold higher risk (95% CI=3.05-6.97) compared with nonproliferative lesions. The risk association was similar but slightly weaker during the post-mammographic era (proliferative lesions without atypia vs. nonproliferative: OR=1.14, 95% CI=0.74-1.76; atypical hyperplasia vs. nonproliferative: OR=3.54, 95% CI=2.14-5.88). When the analysis was stratified by the method of BBD detection, the risk association was similar but slightly attenuated in the stratum of BBDs found on self-exam or physician’s exam (atypical hyperplasia vs. nonproliferative: OR=4.16, 95% CI=2.81-6.16; proliferative without atypia vs nonproliferative: OR=1.54, 95% CI= 1.15-2.07) than in the stratum of BBDs found on mammography (atypical hyperplasia vs. nonproliferative: OR=5.54, 95% CI=2.57-12.0; proliferative without atypia vs nonproliferative: OR=1.15, 95% CI=0.80-3.31). The interaction by calendar time of BBD diagnosis and the method of BBD detection was not statistically significant (p-interaction=0.51 when stratified by pre- (before 1985) vs. post-mammography era (since 1985) and p-interaction=0.09 when stratified by the method of benign breast disease detection). Conclusions: Our data suggest that the risk associated with BBD subtypes initially reported from women biopsied in the pre-mammographic era remain valid for BBD detected after the widespread use of screening mammography was established. Citation Format: Francisco Beca, Hannah Oh, Laura C Collins, Rulla M Tamimi, Stuart J Schnitt. The impact of mammographic screening on the subsequent breast cancer risk associated with biopsy-proven benign breast disease [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 PD3-05.

and case study poster sessions will be conducted during the 2019 College of American Pathologists Annual Meeting (CAP19), which is scheduled for September 21 to 25, 2019. The meeting will take place at the Gaylord Palms Resort & Convention Center, Kissimmee, Florida. The poster sessions will occur in the CAP19 Exhibit Hall. Specific dates and times for each poster session are listed below; “poster focus” times are dedicated poster-viewing periods. Also shown before each poster session are the subject areas that will be presented.

The androgen receptor (AR) is a drug target in breast cancer, and AR-targeted therapies have induced tumor responses in breast cancer patients. In this review, we summarized the role of AR in breast cancer based on preclinical and clinical data. Response to AR-targeted therapies in unselected breast cancer populations is relatively low. Pre-clinical and clinical data show that AR antagonists might have a role in estrogen receptor (ER)-negative/AR-positive tumors. The prognostic value of AR for patients remains uncertain due to the use of various antibodies and cut-off values for immunohistochemical assessment. To get more insight into the role of AR in breast cancer, we additionally performed a retrospective pooled analysis to determine the prognostic value of the AR using mRNA profiles of 7270 primary breast tumors. Our analysis shows that a higher AR mRNA level is associated with improved disease outcome in patients with ER-positive/human epidermal growth factor receptor 2 (HER2)-negative tumors, but with worse disease outcome in HER2-positive subgroups. In conclusion, next to AR expression, incorporation of additional tumor characteristics will potentially make AR targeting a more valuable therapeutic strategy in breast cancer. (C) 2019 The Authors. Published by Elsevier Inc.

PURPOSE: Nutritional factors during different periods in life impact breast cancer risk. Because benign breast disease (BBD) is a well-established risk factor for breast cancer, we investigated childhood nutrition from birth through age 14yr and subsequent BBD. METHODS: A prospective cohort study of 9031 females, 9–15yr at baseline, completed questionnaires (including heights, weights) annually from 1996–2001, in 2003, 2005, 2007, 2010, 2013 and 2014. In 1996, mothers reported infant feeding practices during their daughters’ first year of life. Beginning in 1996, participants completed annual food frequency questionnaires. In 2005, participants (18yr+) began reporting whether they had ever been diagnosed with biopsy-confirmed BBD (N=173 cases). Multivariable logistic regression models estimated associations between childhood nutrition and BBD, adjusted for maternal breast disease and childhood body size factors. RESULTS: Although no infant nutrition factors were associated with biopsy-confirmed BBD, certain adolescent dietary factors were. A multivariable model simultaneously included the most important diet and body size factors from different age periods: higher BBD risk was associated with greater age 10yr consumption of animal (non-dairy, energy-adjusted) fat (OR=2.27, p

PURPOSE: Previous studies suggest that coffee and caffeine intake may be associated with reduced breast cancer risk. To date, there is limited and inconsistent epidemiologic evidence for associations of adolescent diet with mammographic breast density, a strong and consistent predictor of breast cancer. We investigated the association of adolescent caffeine intake with mammographic density in premenopausal women. METHODS: This study included 751 cancer-free women within the Nurses’ Health Study II cohort. Percent breast density (PD), absolute dense (DA) and non-dense areas (NDA) were measured from digitized film mammograms using a computer-assisted thresholding technique; all measures were square-root transformed. Energy-adjusted adolescent caffeine intake was estimated using the data from a food frequency questionnaire. Information regarding breast cancer risk factors was obtained from questionnaires closest to the mammogram date. We used generalized linear regression to quantify associations of caffeine intake with breast density measures. RESULTS: In multivariable analyses, adolescent caffeine intake was not associated with any of the density phenotypes (caffeine 4(th) vs. 1(st) quartile: β=−1.27, 95% CI −4.62; 2.09, p-trend=0.55 for percent density; β=−0.21, 95% CI −0.76, 0.34, p-trend=0.65 for absolute dense area, and β=0.23, 95% CI −0.28, 0.74, p-trend=0.50 for non-dense area). Additional adjustment of the models for body mass index at age 18 resulted in attenuation of the risk estimates. CONCLUSIONS: Our findings do not support the hypothesis that adolescent caffeine intake is associated with premenopausal mammographic breast density.

PURPOSE: Little is known about how a breast cancer diagnosis and treatment affects job-related outcomes in young women with breast cancer, who are an integral part of the workforce. We sought to describe employment trends among young breast cancer survivors. METHODS: 911 women with non-metastatic breast cancer were surveyed about employment-related outcomes 1-year post-diagnosis. Participants were enrolled in the Young Women’s Breast Cancer Study an ongoing, multi-center cohort of women diagnosed with breast cancer at age ≤40. RESULTS: Among 911 women, median age at diagnosis was 37 years (range: 17–40). Most women (80%, n=729) were employed 1-year post-diagnosis. Among the 7% (n=62) employed before diagnosis but who reported unemployment at 1-year, approximately half reported they were unemployed for health reasons. Among employed women, 7% said treatment affected their ability to perform their job. Women with stage 3 disease (vs. stage 1 disease, odds ratio (OR): 3.73, 95% CI, 1.39–9.97) and those who reported having money to pay bills after cutting back or difficulty paying bills at baseline (vs. having enough money for special things, OR: 2.70, 95% CI, 1.32–5.52) at baseline were more likely to have transitioned out of the workforce. CONCLUSIONS: Our results suggest an impact of disease burden and socioeconomic status on employment in young breast cancer survivors. There is a need to ensure young survivors who leave the workforce following diagnosis are sufficiently supported given the potential adverse psychosocial and financial impacts unemployment on survivors, their families, communities, and society.

Background Epidemiologic data suggest that parity increases risk of hormone receptor-negative breast cancer and that breastfeeding attenuates this association. Prospective data, particularly on the joint effects of higher parity and breastfeeding, are limited. Methods We investigated parity, breastfeeding, and breast cancer risk by hormone-receptor (estrogen (ER) and progesterone receptor (PR)) and molecular subtypes (luminal A, luminal B, HER2-enriched, and basal-like) in the Nurses’ Health Study (NHS; 1976–2012) and NHSII (1989–2013). A total of 12,452 (ER+ n = 8235; ER− n = 1978) breast cancers were diagnosed among 199,514 women. We used Cox proportional hazards models, adjusted for breast cancer risk factors, to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results Parous women had lower risk of ER+ breast cancer (vs. nulliparous, HR = 0.82 [0.77–0.88]); no association was observed for ER− disease (0.98 [0.84–1.13]; Phet = 0.03). Among parous women, breastfeeding was associated with lower risk of ER− (vs. never 0.82 [0.74–0.91]), but not ER+, disease (0.99 [0.94–1.05]; Phet

Background: Synchronous bilateral breast cancer is rare, with reported incidence from 0.3-12%; the incidence and pattern of bilateral breast cancer among younger women is unknown. Here we report the incidence and phenotypes of bilateral breast cancer in women ≤40 years of age enrolled in the Young Women's Study (YWS) cohort. Methods: The YWS is a multi-center, prospective cohort study that enrolled women with newly diagnosed breast cancer at age ≤40 years from 2006-2016. Those with synchronous bilateral breast cancer (in-situ and/or invasive) formed our study cohort. Disease characteristics and treatment were obtained by medical record review. Central pathology review was performed to capture histologic features and categorize the tumor phenotype as either luminal A (hormone receptor (HR)+, HER2-, grade 1 or 2), luminal B (HR+, HER2+, or HER2- and grade 3), HER2-type (HR-, HER2+), or triple negative (TNC; HR/HER2-). Tumor phenotypes of bilateral breast cancers were compared and evaluated for concordance. Results: Among 1302 patients enrolled in the YWS, 20 (1.5%) patients presented with bilateral disease, with median age of diagnosis of 38 years (range 18-40). The majority of patients (13 (65%)) presented with unilateral symptoms and contralateral disease was identified on subsequent imaging. 12 (60%) reported a positive family history of breast cancer and 17 (85%) underwent genetic testing; resulting in the identification of 6 mutation carriers (2 BRCA1, 3 BRCA2, 1 TP53). The majority of patients (15 (75%)) underwent bilateral mastectomy, 1 underwent unilateral mastectomy with contralateral lumpectomy, and 4 underwent bilateral lumpectomy. On pathology, 2 patients had bilateral in-situ disease, 5 had unilateral invasive and contralateral in-situ disease, and 13 had bilateral invasive disease. Of those with bilateral invasive disease, all had concordant tumor histology (92% ductal, 8% ductal and lobular), 10 (77%) patients had bilateral luminal tumors and when fully characterized 6 were of the same luminal type. Only one patient had bilateral basal-like breast cancer. Patient ID ERPRHer2 amplifiedGradePhenotype1Left++-2Luminal A Right++-3Luminal B3Left++-3Luminal B Right++-3Luminal B6Left++-3Luminal B Right++-3Luminal B9Left++-2Luminal A Right++-2Luminal A10Left+++3Luminal B Right++-2Luminal A12Left+--3Luminal B Right+--2Luminal A13Left---NABasal-like Right++-NALuminal A or B14Left+++2Luminal B Right++-3Luminal B15Left++-3Luminal B Right+++3Luminal B16Left+++3Luminal B Right--+NAHEr2-type17Left---3Basal-like Right---3Basal-like19Left++-2Luminal A Right++-3Luminal B20Left++-1Luminal A Right++-2Luminal A Conclusions: Among a large cohort of young women, only 20 (1.5%) had bilateral disease, and the majority of the invasive tumors were of the luminal phenotype, yet frequently differed by grade or HER2 status; supporting the need for thorough pathologic evaluation of bilateral disease to determine risk and tailor treatment. Overall the low incidence of bilateral disease and preponderance of the luminal phenotype in this population is reassuring. Citation Format: Pak LM, Rosenberg SM, Ruddy KJ, Tamimi RM, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Snow C, Collins L, King TA, Partridge AH. Tumor phenotype and concordance in synchronous bilateral breast cancer in young women [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 P6-22-03.

Background: Our understanding of mediators of immune infiltration in breast cancer and normal breast tissue remains limited. We hypothesize that patient factors known to be associated with inflammation and immune subsets, including body mass index, alcohol intake, and age and diagnosis, may play an important role in the tumor-immune microenvironment. Analyses of immune gene expression and signatures facilitate interrogation of the immune microenvironment in large patient cohorts. Methods: Participants from the Nurses' Health Study cohorts I and II diagnosed with invasive breast cancer were included. Total RNA extracted and microarray performed for 882 tumor and 695 tumor-adjacent samples, of which 623 tumors have matched tumor-adjacent data. CD8+ T-cell expression metrics were assessed: CD8A single gene expression (CD8Agene), a CD8 T-cell signature (CD8sig), and a tumor infiltrating lymphocyte signature derived from the GeparSixto clinical trial (GSAct). Standard clinicopathologic features were evaluated, as well as body mass index (BMI) one year prior to diagnosis, cumulative average alcohol intake, and age at diagnosis. Results: Overall, tumor and adjacent normal tissue demonstrated positive correlation of CD8Agene, CD8sig, and GSAct (n=623 pairs, Pearson's r = 0.46, 0.36, 0.31, respectively; all p Conclusion: In this cohort of over 600 tumor:normal pairs and a separate validation cohort, multiple distinct CD8+ T-cell expression metrics are correlated between breast cancer and tumor-adjacent normal breast tissue. This suggests that the adjacent normal breast may reflect an altered immune microenvironment in the context of breast cancer. While age at diagnosis and alcohol intake are not significantly associated with tumor CD8 expression metrics, BMI was significantly associated with tumor CD8Agene expression in a multivariate model. Citation Format: Damicis A, Heng YJ, Kensler K, Asad S, Adams E, Singh J, Zhang Y, Nock W, Wesolowski R, Williams N, Reinbolt R, Sardesai S, VanDeusen J, Noonan A, Lustberg MB, Ramaswamy B, Eliassen AH, Hankinson SE, Tamimi R, Stover DG. CD8+ T-cell gene expression and signatures in breast cancer and adjacent normal breast tissue: Association with body mass index, alcohol intake, and age at diagnosis [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 P1-09-01.

Background: Young women with breast cancer (BC) are increasingly choosing contralateral prophylactic mastectomy (CPM), yet little is known about the impact of surgical choices on quality of life (QOL) and psychological health. Using a large, prospective cohort of young women with BC, we sought to evaluate psychosocial outcomes following surgery. Methods: Among participants of the Young Women's BC Study, a multi-center cohort of women dx'd with BC at age ≤40, we identified women with Stage 0-3 unilateral BC who had surgery and completed surveys that included measures of QOL (CARES) and psychological health (HADS). Linear mixed-effects models were fit to assess changes from 1 to 3 years (yrs) post-dx in anxiety, depression, psychosocial, body image, and sexual scores. Adjusted (stage, hormone receptor status, chemotherapy, age) means were estimated and differences compared (Bonferroni adjusted p-values) between CPM vs breast conserving surgery (BCS) and unilateral mastectomy (UM) at 1, 2, and 3 yrs. Results: Of 863 women, 30% had BCS, 24% UM, 46% CPM. Median age at dx was 37 (range: 22-40). Of women who had UM/CPM, 84% had reconstruction. Among women who had CPM, mean body image (p=.02), psychosocial (p Conclusions: While psychosocial health improves over time, differences by surgery persist, with women who have CPM experiencing more sexual and body image issues compared to women who undergo BCS or M in the years following surgery. Given that surgical choices may be affected by distress experienced before or at dx, ensuring young women receive adequate support when making surgical decisions as well as after surgery is warranted. Mean CARES and HADS scores Year 123Psychosocial*CPM.89.78.76 UM.75.69.66 BCS.72.65.66 Sexual*CPM1.641.371.40 UM1.411.291.08 BCS1.181.071.04 Body image*CPM1.331.221.30 UM1.161.131.04 BCS.64.57.56 Anxiety**CPM7.657.406.79 UM6.505.916.39 BCS7.036.226.50 Depression**CPM3.723.213.25 UM3.022.802.70 BCS3.332.823.13**CARES range: 0-4;higher scores=worse QOL **HADS range 0-21;higher scores=more anxiety/depression Citation Format: Rosenberg SM, Hu J, Dominici LS, Poorvu PD, Ruddy KJ, Tamimi RM, Schapira L, Come S, Peppercorn JM, Borges VF, Partridge AH. Longitudinal changes in psychosocial health in young women following breast cancer surgery: Results from a multi-center 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 P2-14-03.

Background: The 21-gene Recurrence Score (RS) assay is prognostic among women with early-stage estrogen receptor (ER) positive and human epidermal growth factor receptor 2 (HER2) negative breast cancer (BC) and is used to select patients for chemotherapy (CT). Young women (age Methods: In the Young Women's Breast Cancer Study, a prospective cohort study of women diagnosed with BC at age 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 years. Median age at diagnosis was 37, most had N0 BC (300/509, 59%), and the majority had RS 11-25 (306/509, 60%). RS result was significantly associated with DRFI in N0 BC, with hazard ratio (HR) (95% CI) of 0.29 (0.07,1.30) and 0.21 (0.09,0.50) for RS26 (and trended towards significance in N1 BC). Results were similar using conventional RS groups. Among women with N0 BC and RS 11-25, 44% received CT, with two events in the 86 receiving CT (2.3%) and 6 events in the 109 without CT (5.5%); 5/8 (63%) occurred in those with RS 20-25. Table 1 N0N1Total Cohort N%N%N% 3005916332509100Median Age37.137.537.2Tumor Stage T120869694229358T28227784817635T3103159357T4001151Grade I4716855711II16555794926652III8829754618536Not assessed 1 1 PR status by IHC Negative (=1%)280931469047092Chemotherapy No1414712715430Yes159531519335570Ovarian Suppression No263881499145289Yes37121495711TAILORx RS Groups RS =267224613714929Conventional RS Groups RS =31481640259919 Table 2 6-year freedom from distant recurrence or breast cancer deathDRFI HR (95% CI) N0N1N0N1TAILORx RS Groups RS =2685.1%71.3%RefRefConventional RS Groups RS =3186.4%62.8%RefRef Conclusions: The RS is prognostic among young women with node-negative and node-positive BC, and is a valuable tool for risk stratification. Disease outcomes among young women with N0 disease and RS 11-25, a minority of whom received CT, are very good. Evaluation of the effect of ovarian suppression/CT-induced amenorrhea by RS/treatment strata is ongoing. Citation Format: Poorvu PD, Gelber SI, Rosenberg SM, Ruddy KJ, Tamimi RM, Collins LC, Peppercorn J, Schapira L, Borges VF, Come SE, Warner E, Jakubowski DM, Russell C, Winer EP, Partridge AH. Prognostic impact of the 21-gene recurrence score assay among young women with node-negative and node-positive ER+/HER2- 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 P2-08-07.