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P4-11-10: Perceptions, Knowledge and Satisfaction with Contralateral Prophylactic Mastectomy among Young Women with Breast Cancer.

Background: There has been an increasing prevalence of contralateral prophylactic mastectomy (CPM), particularly among younger women with breast cancer. There has been limited research evaluating patient preference, knowledge and decision-making regarding this issue. Methods: We surveyed women who had bilateral mastectomy who were enrolled in a multicenter, longitudinal cohort study of women diagnosed with breast cancer at age 40 and younger. The CPM survey included 23 items on decision making, knowledge, and satisfaction with CPM. Results: Of the 550 patients enrolled as of November 2010, 157 (28.5%) had bilateral mastectomy, of whom 124 completed the CPM survey (response rate 79%). Women with bilateral breast cancer (3) or bilateral prophylactic (1) indications for surgery were excluded. Median age at diagnosis was 37 years (range 26–40); 26 women (21%) reported having a genetic mutation (21 BRCA1 and 5 BRCA2). Excluding mutation carriers, women estimated that a median of 10 of 100 women (range 0–90) would develop contralateral breast cancer in the 5 years after unilateral breast cancer treatment and that 5 of 100 women (range 0 — 98) treated with CPM would develop contralateral breast cancer. Eighteen percent of all respondents believed that women who undergo bilateral mastectomy live longer. Women were asked the importance of potential reasons for undergoing CPM (see Table 1). Eighty-two percent of women were “extremely confident” in their decision to undergo CPM and 92% would “definitely” still choose CPM. Conclusion: Young women with breast cancer have high rates of CPM. Many young women who have undergone CPM overestimate the risk of contralateral disease and the benefits of CPM, including believing that CPM will prevent metastasis and extend life. Interventions to counsel young women with early breast cancer to help them make optimal surgical treatment decisions are needed. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-10.

Pathologic Features and Biomarker Expression among Young Women with Breast Cancer: Results from the Young Women's Breast Cancer Study.

Background: Prior studies have suggested a higher prevalence of high grade, ER-negative and HER2-positive tumors as well as basal-like carcinomas in young women with breast cancer; features that are associated with a more aggressive phenotype and decreased survival. However, studies are limited by small numbers among the very young ( Design: The Young Women9s Breast Cancer Study is an ongoing multi-center prospective cohort enrolling women with newly diagnosed breast cancer at age ≤ 40 years old. Medical records are reviewed for clinical characteristics, tumor stage and receptor status. HER2 positivity is defined as IHC 3+ or FISH amplified. Pathologic features are examined by central review, with detailed evaluation of phenotypic features associated with basal-like carcinomas. Univariate logistic regression models were used to evaluate the relationship to age, as a continuous variable and each clinico-pathologic feature. Results: The first 248 women for whom pathology has been reviewed (71% of participants enrolled to date) are included in this analysis. The table below presents the distribution of pathologic features by age group. There are no statistically significant differences in ER expression, PR expression or HER2 overexpression by age at diagnosis. Nor are the youngest women more likely to have higher stage or higher grade tumors. However, the youngest women are more likely to have pushing tumor margins and zones of tumor necrosis (p=0.03 and p=0.01 respectively). Conclusion: We find no differences in the distribution of poor prognostic features such as higher tumor stage, high tumor grade, ER/PR negativity or HER2 positivity among the very young. However, our study does indicate that the youngest women are significantly more likely to have tumors with pushing margins and zones of tumor necrosis, which are some of the morphologic features associated with the basal-like phenotype. Further research is warranted to evaluate the implication of these findings with regard to the etiology, treatment and prognosis of breast cancer in young women. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6007.

Abstract P2-09-07: Drugs don't work if people don't take them: Non-initiation of endocrine therapy in young women

Background: Despite the well-established survival benefit associated with adjuvant hormonal treatment, younger women with hormone receptor positive (HR+) breast cancer (BC) are less adherent to endocrine therapy (ET) as prescribed, compared to their older counterparts, and may have unique issues that contribute to ET non-adherence. In an effort to identify factors that can be targeted to improve ET uptake and adherence, we sought to evaluate ET initiation in young women with BC. Methods: As part of a multi-center, prospective cohort enrolling women with newly diagnosed BC at age ≤40 years between 2006-2016, we identified 657 women with HR+, Stage 0-III BC. Participants complete serial surveys that included questions about socio-demographics, fertility concerns, and treatment. Women who did not report taking tamoxifen or an aromatase inhibitor (AI) at least once in the 18 months after diagnosis (dx) were classified as non-initiators. Variables significant at p Results: By 18 months post-dx, 15% (99/657) had not initiated ET; among women with Stage 0 BC, 77% (51/66) had not initiated vs 8% (48/591) with invasive BC (p Conclusion: Most young women with HR+ DCIS do not take adjuvant ET despite the potential benefits (substantially reduced risk of local recurrence and contralateral BC) and very low risk of serious toxicity. Among young women with invasive HR+ BC, a significant minority fails to start ET within 18 months of dx. Adjuvant ET non-initiation may contribute in part to the racial and SES outcomes disparities that have been observed. Further study is needed to elucidate barriers to initiation with the goal of developing targeted interventions that will enhance ET initiation and adherence in general. Citation Format: Rosenberg SM, Gelber S, Ruddy KJ, Tamimi RM, Schapira L, Borges VF, Come S, Meyer ME, Partridge AH. Drugs don9t work if people don9t take them: Non-initiation of endocrine therapy in young women [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-09-07.

Abstract P4-10-04: Employment trends in young women following a breast cancer diagnosis

Background: Workplace concerns are particularly salient for young women with breast cancer (BC), and a cancer diagnosis (dx) and treatment may affect their careers. We sought to evaluate the perceived impact of dx on employment, describe job changes, and identify factors associated with transition out of the workforce after dx of BC at a young age. Methods: As part of an ongoing, multi-center cohort of young women diagnosed with BC at age ≤ 40, we surveyed women with early-stage BC about their pre- and post-dx employment status. Additional items assessed socio-demographic and treatment information; tumor characteristics were ascertained via pathology and medical record review. We used logistic regression to identify predictors of transitioning from pre-dx employment to unemployment at 1 year after dx. Among women employed 1 year after dx, we evaluated job satisfaction, perceived impact of dx on job performance, accommodations made by employers, and perceived likelihood of employment in the future. Results: 76% of women (555/730) were employed both before dx and at 1 year; 13% were not employed at either time point; 7% were employed pre-dx but unemployed at 1 year; 4% were not employed prior to dx but reported employment at 1 year. Among women employed 1 year after dx, 74% (427/581) were somewhat or completely satisfied with their job. Only 6% said cancer or treatment limited their ability to perform their job quite a bit or very much; 38% said their ability was affected a little bit. Most (63%) said their employers had made accommodations for them, and almost all women (93%) said it was very likely they would be working in 1 year. In multivariable analyses (Table 1), women with stage 3 disease (vs. stage 1), were more likely to transition out of the workforce following dx, while women with a college or graduate degree (vs. no college degree) were less likely to transition out. Conclusion: Most young women with early stage BC remain employed and report a willingness by their employer to make accommodations following a breast cancer dx. While few women reported that their dx or treatment limited their job performance, the finding that women with more advanced disease were more likely to transition out of the workforce suggests an impact of dx/treatment burden on employment. Women without a college degree were also at risk for unemployment post-dx, suggesting that job type, socioeconomic status, and environment affect employment outcomes. Attention to these subgroups of women is warranted to ensure that they are sufficiently supported given the potential adverse psychosocial and financial impacts of unemployment on patients, families, communities, and society. Citation Format: Partridge AH, Rosenberg SM, Rajagopal PS, Ruddy KJ, Tamimi RM, Schapira L, Come S, Borges V, Gelber S. Employment trends in young women following a breast cancer diagnosis. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P4-10-04.

Abstract P4-17-01: Attitudes of medical oncologists towards research breast biopsies in patients with newly diagnosed stage I-III breast cancer not enrolled in a clinical trial

Background: Patients (pts) with breast cancer treated with neo-adjuvant therapy on clinical trials are often asked to consent to pre-treatment and on-treatment research biopsies. There is increasing interest in obtaining tissue samples at similar time points in pts treated with neo-adjuvant therapy outside of clinical trials. However, medical oncologists’ (MOs) attitudes towards approaching pts about research biopsies in this setting are unknown. Methods: Three hundred and nine academic breast MOs identified from websites of the National Cancer Institute (NCI) – designated cancer centers were asked to complete a survey either by paper or online. Eligible MOs (MOs who saw breast cancer pts and who saw pts >4 hours/week.) were asked to predict what proportion of their pts with newly diagnosed, non-metastatic breast cancer would consent to research purposes only biopsies (RPOBs) i.e., biopsies with no clinical benefit to pt. Median values are reported. Two-sided Fisher’s exact test was used to compare categorical variables using a α level of .05. Results: Of 221 (101F,85M, 5 unknown) MOs who completed the survey, 30 MOs were ineligible (response rate=221/309,72%). Median age was 50 (Range 33-80). Median years of oncology experience was 15 (Range 1-45). MOs predicted that 14%, 63% and 21% of their pts would definitely/probably, maybe, probably not/definitely not consent to a RPOB of the breast. Forty-one percent, 34%, 19%, 3% of MOs were very comfortable, somewhat comfortable, somewhat uncomfortable, and very uncomfortable asking pts to consent to RPOBs respectively. The only factor associated with increased comfort discussing an RPOB was MOs’ years in practice. MOs with fewer years ( 15 years) (Adjusted RR=1.2, p =0.02). Gender, number of pts enrolled onto clinical trials, and MOs with pts who had research biopsies in the last 3 months was not associated with increased comfort. MOs who were more comfortable in approaching pts for RPOBs were associated with estimating a larger proportion of their pts as willing to undergo RPOB. For example, nearly one third of MOs who were very comfortable with approaching pts for RPOBs estimated that greater than 50% of their pts would consent to research biopsies. In contrast, nearly all the MOs who were very uncomfortable with approaching pts for RPOBs estimated that less than 25% of their pts would consent to research biopsies. The 3 most common reasons why MOs were reluctant to consent pts for a RPOB include pain/discomfort of a biopsy (59%), risk of a biopsy procedure complication, (44%), and inconvenience to the pt (33%). Conclusions: Academic breast MO’s predicted that fewer than 1 in 5 women with newly diagnosed, non-metastatic breast cancer would definitely or probably agree to a request for an RPOB outside of the context of a therapeutic trial, and approximately one-quarter of MOs expressed discomfort in approaching pts for such procedures. Our results have important implications regarding the feasibility of such research efforts, and identify potential barriers to target for intervention. Citation Format: Davinia SE Seah, Sarah Scott, Hao Guo, Julie Najita, Ruth Lederman, Elizabeth Frank, Jessica Sohl, Zsofia Stadler, Stuart G Silverman, Jeffrey Peppercorn, Eric P Winer, Steve E Come, Nancy U Lin. Attitudes of medical oncologists towards research breast biopsies in patients with newly diagnosed stage I-III breast cancer not enrolled in a clinical trial [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-17-01.

PD04-05: Body Image Issues in Young Breast Cancer Patients: The Impact of Chemotherapy, Hormone Treatment, and Surgery.

Background: While there is evidence that younger women with breast cancer are more likely to experience compromised quality of life compared to older women, few studies have prospectively explored the impact of treatment, including surgery, chemotherapy, and hormone therapy, on body image, in particular, in very young women (≤40 years old). This analysis examined treatment-associated differences in self-reported body image among a large cohort of young women diagnosed with breast cancer. Methods: 431 women enrolled in an ongoing multi-center prospective cohort study with Stage 0-Stage III breast cancer were included in this analysis. Body image was measured at baseline (1-12 months following diagnosis) using three items from the Cancer Rehabilitation Evaluation System (CARES) survey. CARES scores range from 0–4, with higher scores indicative of greater image concerns. Mean differences in CARES scores between treatment groups (chemotherapy within the last month vs. none; hormone therapy vs. none; lumpectomy vs. mastectomy alone vs. mastectomy + reconstruction) were estimated using T-tests and one-way ANOVA. To control for concurrent treatment, stage, and time since diagnosis, multiple linear regression models were fit and least squares means estimated and compared between treatment groups. Multiple comparisons were adjusted for using the Bonferroni correction. Results: Median age at diagnosis was 37 (range: 17–40) and median time from diagnosis to study enrollment was 5 months (range: 1–12 months). In the unadjusted analysis, there were no significant differences in scores between women who had received chemotherapy within the last month and those who did not (p=0.80), while women who reported hormone treatment had higher mean CARES scores compared to women who did not (p=0.04). Among women who had undergone surgery (n=370), women who had lumpectomies had a mean CARES score of 0.95, which was significantly lower (p Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr PD04-05.

P4-11-12: Molecular Phenotype of Breast Cancers in a Large Cohort of Young Women According to Time Interval Since Pregnancy.

Abstracts: Thirty-Fourth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 6‐10, 2011; San Antonio, TX Background: The increase in breast cancer risk during pregnancy and post partum is well recognized. The cross-over to protective effect does not occur until many years later and varies with age at first birth. Recently, a genomic signature specific to the pregnant compared with the non-pregnant breast has been identified; this signature remains present in the postmenopausal parous breast. Given this, we investigated whether time interval since pregnancy affects the phenotype of breast cancers arising in young women compared with nulliparous women. Methods: We examined molecular phenotype, according to histologic grade and biomarker status, in relation to time since pregnancy in an ongoing prospective cohort study (n=355) of young women (≤40yrs) with breast cancer. Medical records were reviewed for tumor stage and receptor status. Parity was ascertained from questionnaires completed within 9 months of diagnosis. Tumor grade was determined by central pathology review. Using tumor grade and biomarker expression, cancers were categorized as luminal A (ER+ and/or PR+, HER2−, histologic grade 1 or 2); luminal B ( ER+ and/or PR+, HER2+, or ER and/or PR+, HER2− and grade 3); HER2 type (ER-, PR-, HER2+); and triple negative (ER-, PR-, HER2−). Results: The median age of the study population is 37 years (range 17–40). Overall, 80% of women had stage 1 or 2 disease; 67% of cancers were ER positive and 32% showed HER2 overexpression. The distribution of breast cancer molecular phenotypes by time interval since last pregnancy is shown in the table. Distribution of molecular phenotype by interval between last pregnancy and diagnosis ![Graphic][1] In our large cohort of parous young women, we found no differences in the distribution of molecular phenotype according to time interval since pregnancy. However, nulliparous young women were more likely to develop luminal A cancers compared to parous women (40% vs. 29%; unadjusted chi square p-value=0.03) and appeared less likely to develop HER2−type and triple negative cancers (7% vs. 13%, p-value=0.09 and 17% vs. 23%, p-value=0.22 respectively). There were no differences in the distribution of luminal B cancers. Conclusions: The distribution of molecular phenotypes is similar among parous young women regardless of the time interval since parturition. Nulliparous young women appear more likely to develop luminal A cancers compared to parous women. Whether the difference in molecular phenotypes of pregnancy-associated breast cancers vs. cancers arising in nulliparous women is due to the effects of genomic alteration remains to be investigated. Effects of a prior pregnancy appear consistent across a 5-year period, in keeping with the concept of genomic alterations identified in the normal pregnant breast and thereafter. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-11-12. [1]: /embed/inline-graphic-1.gif

Dose-Dense (dd) Doxorubicin and Cyclophosphamide (AC) Followed by Weekly Paclitaxel (P) with Trastuzumab (T) and Lapatinib (L) in Early Breast Cancer (EBC); Troponin I and C-Reactive Protein as Biomarkers of Cardiotoxicity.

BackgroundThe early detection of cardiotoxicity and congestive heart failure (CHF) from anthracyclines and anti-HER2 agents is currently limited to measuring changes in left ventricular ejection fraction (LVEF) at arbitrary time points. This approach has limited sensitivity and specificity and has led to the investigation of putative biomarkers such as cardiac Troponin I (TnI), a highly specific marker of myocardial damage and C-reactive protein (CRP), a sensitive inflammatory marker. In a pre-planned analysis we investigated these as biomarkers of cardiotoxicity within a prospective study testing the feasibility of ddAC- followed by weekly P with T and L.Materials and MethodsPatients (pts) with HER2+ EBC enrolled at MSKCC and DF/HCC and received ddAC (A 60mg/m2 + C 600mg/m2) x 4 → weekly P (80mg/m2) x 12 + T + L (1000mg/day). T+L continued for a total of 1yr. At baseline pts had LVEF ≥50%. Pts with unstable angina, CHF, recent MI, uncontrolled arrhythmia, grade 3 QT prolongation were excluded. LVEF was assessed by MUGA scan at mths 0, 2, 6, 9 and 18. TnI and CRP were measured every 2 wks right before treatment (Rx) during ddAC-PTL, then at mths 6, 9 and 18. TnI was categorized as “undetectable” ( 0.31ng/ml). Elevated CRP was defined as (>0.8mg/dl; MSKCC, >0.3mg/dl; DF/HCC). Investigators were blinded to these results until pts completed 18mth follow-up (F/U).ResultsFrom Apr 07- Apr 08, 95 pts were enrolled; 39/95 (41%) withdrew due to PTL toxicities (incl. 3 with asymptomatic LVEF (aLVEF) declines and 3 with CHF). Final biomarker results were available in 84 pts (88%) and 11 pts (12%) continue on study. During Rx, minimal elevations in TnI occurred in 55 pts (65%). One pt had ↑TnI above normal range with AC#4; MUGA 1 wk later was unchanged (LVEF 75%), but she died from sepsis during subsequent Rx without evidence of CHF. Elevations in TnI occurred only during chemoRx and no pt had a ↑TnI during TL or at 18mth F/U. Of 55pts with elevated TnI, 25 (45%) had aLVEF declines (3 ↓ ≥16%, 10 ↓ 10-15%, 12 ↓ 5 Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3088.

Prevalence and Predictors of Distress in Young Women with Newly Diagnosed Early Stage Breast Cancer.

Background: Previous research suggests that young women are at high risk for psychological distress after a breast cancer diagnosis. We sought to identify factors associated with overall distress, anxiety, and depression in this vulnerable population.Materials and Methods: We have surveyed women age ≤40 with recently diagnosed stage I-III breast cancer in an ongoing prospective multi-center cohort study started in late 2006. The baseline survey includes the Hospital Anxiety and Depression Scale (HADS) as well as sociodemographic and medical history items. Medical record and central pathology review were also performed. Women with HADS scores >14 were considered distressed, and those with scores >10 on the anxiety or depression subscales were considered anxious or depressed, respectively. We conducted multivariate logistic regression modeling to determine predictors of anxiety, depression, and overall distress.Results: The first 258 eligible women who completed the baseline survey are included in this analysis. Median age at diagnosis was 37 years. Seventy-six percent were married, 90% white, 83% college educated, 66% had children, 99% were medically insured, and 60% were employed full time prior to diagnosis. Fifty-two percent of women reported their finances as comfortable. Forty-eight percent reported a household income over

Variation in the Attitudes of Medical Oncologists Toward Research Biopsies in Patients With Metastatic Breast Cancer

100,000 per year, and only 15% reported an income less than