Ah Partridge

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 P2-15-01: Long-Term Risk Perceptions and Quality of Life of Women with Ductal Carcinoma In Situ

Background: Research has demonstrated that many women with ductal carcinoma in situ (DCIS) overestimate their risk of future breast cancer events. However, no prior studies have evaluated risk perceptions in long-term follow-up. Methods: As part of a multicenter longitudinal cohort study, we mailed long-term follow-up surveys to 315 of 392 women who had previously responded to a survey 18 months after they were diagnosed with DCIS (33 of the 392 were excluded because they were receiving follow-up care at outside centers, and 44 because of recurrence/death). We evaluated psychosocial distress by Hospitalized Anxiety and Depression Scale (HADS) and Revised Impact of Events Scale (RIES), quality of life (QOL) by Short Form Health Survey (SF-36), and risk perceptions with items used previously in the cohort. Results: One hundred ninety-three women (61%) responded. They were a median age of 53 yrs (range 31-89) and a median of 5.8 yrs from diagnosis (range 4.3-7.0). Twelve were excluded due to report of recurrence. Of the 181 remaining, 32% perceived at least a moderate risk of developing DCIS again within 5 yrs; 43% perceived at least a moderate lifetime risk of developing DCIS again; 27% perceived at least a moderate risk of developing invasive breast cancer within 5 yrs; 38% perceived at least a moderate lifetime risk of developing invasive breast cancer; 24% perceived at least a moderate risk of DCIS spreading to other parts of their bodies. For qualitative responses of ≥ moderate perceived risk, median quantitative risk perception was 10% regarding 5-yr risk of DCIS or invasive cancer, 20% regarding lifetime risk, and 50% pertaining to risk of DCIS spreading. The proportion of women reporting ≥ moderate perceived risk of DCIS spreading remained stable over time (25% at baseline; 26% at 18 mos), but this proportion decreased for other perceptions of risk (e.g., at baseline and 18 mos, 51% and 50% of these same women perceived ≥ moderate risk of developing DCIS again within 5 yrs). In a multivariable model, worse financial status (OR 2.6, 95% CI 1.3-5.3) and higher perceived risk on earlier surveys (OR 24.4, 95% CI 12.7-47.2) were the only predictors of ≥ moderate perception of risk of DCIS spreading to other parts of the body in long-term follow-up. Non-significant covariates included age, race, education, grade of DCIS, comedonecrosis, mastectomy, radiation, marital status, employment status, comorbidity, and HADS and RIES scores. This contrasted with earlier survey data, which demonstrated an association between higher risk perceptions and anxiety by HADS and RIES. In long-term follow-up, only 7% were found to be anxious (HADS Anxiety ≥11) and 0.6% were depressed (HADS Depression ≥11). Median SF-36 scores were 48.9 (range 15.7-58.2) and 47.1 (range 23.6-60.3) for the physical and mental components, respectively, consistent with overall good QOL. Conclusions: Women with a history of DCIS continue to harbor inaccurate perceptions of risk of future breast cancer events even at 6 yrs follow-up. Future research should evaluate how these excessive risk perceptions impact health behaviors. Interventions to improve risk perceptions are warranted. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-15-01.

The Quality of Decisions about Adjuvant Chemotherapy for Early Stage Breast Cancer.

Background: Decisions about adjuvant chemotherapy are highly challenging for many women with early stage breast cancer. We sought to assess the quality of breast cancer patients9 decisions about chemotherapy by measuring their knowledge and the degree to which their treatment decisions reflect their goals and preferences.Methods: We mailed a survey to early stage (I, II) breast cancer survivors who were treated at one of four sites, as part of a larger study to validate decision quality instruments. A subset of women completed the chemotherapy module, which included questions about the patient-provider interaction, about facts, about treatment goals, and about the patient9s preferred treatment. Characteristics associated with knowledge were identified with linear regression. Characteristics associated with chemotherapy were identified with logistic regression.The percentage of patients who received their preferred treatment was calculated.Results: 358 patients completed the survey (response rate 59%). 64% of patients had Stage I disease, and 57% had chemotherapy. Average age was 56.9 years, 82.6% were white, and 63.7% had a college degree.Decision making: 70% of patients reported that their provider mentioned chemotherapy as an option. 43% reported that their provider asked for their preference about chemotherapy. 23% said the doctor mainly made the decision, 29% said they mainly made the decision, and 46% said both made the decision.Most women (92%) felt their level of involvement was about right.Knowledge: The mean knowledge score was 39.6% (SD 20.3). 29.9% knew that less than half of women with early stage breast cancer eventually die from breast cancer without chemotherapy or hormone therapy.21.8% knew that more than half are free from recurrence in 10 years without chemotherapy or hormone therapy. Chemotherapy treatment and the doctor having discussed chemotherapy were significantly associated (p Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 2083.

Abstract P1-07-05: Integrated transcriptional analysis of the triple negative 'proliferation paradox': High proliferation, chemosensitivity, and poor prognosis

Background: In triple-negative breast cancers (TNBC), high proliferation is associated with greater chemosensitivity but, paradoxically, also associated with poor prognosis. We hypothesized that this subset of TNBC has distinct transcriptional features that contribute to poor prognosis. Approach: To evaluate transcriptional signatures associated with this 9proliferation paradox,9 we identified 17 study cohorts of TNBC treated with neoadjuvant chemotherapy (NAC) that reported receptor status, pathologic response, and had expression data from biopsies obtained prior to NAC (n=446). In 6 studies, distant metastasis-free survival (DMFS) data was available for 235 patients with a median follow-up of 31.2 months. We calculated scores for 135 published gene expression signatures for each tumor and evaluated the association with response to chemotherapy and DMFS. Results: Using recursive partitioning to develop a model of response using a training set (n=340), six of the 135 expression signatures stratify primary tumors into four groups based on signatures of proliferation, BRCA1 mutation, immune, luminal, Ras, and PI3K phenotypes (Table 1.). Response to NAC ranged from 11% to 61% pCR/RCB-I and results were highly concordant when applied to a validation set (n = 106, p = 0.006). The group that was highly proliferative but chemoresistant (9resistant9 group) had a distinct transcriptional profile, including lower 9BRCA-ness9 and DNA damage expression signatures with higher Ras and stem cell signatures. The 9resistant9 group had the poorest DMFS (HR 2.48 [1.52-4.06]; log-rank p=0.002) and this poor survival was validated among chemotherapy-treated TNBCs in a separate dataset, METABRIC. Analyses of only patients with residual disease after NAC demonstrated that the 9resistant9 group remained poorest prognosis, with median DMFS of only 31 months from diagnosis. Conclusions: Using a novel approach to categorize primary TNBC tumors based on six signatures, we can effectively distinguish subgroups with higher versus lower pCR rates. One specific group demonstrated high proliferation but low response to chemotherapy and particularly poor survival. This group demonstrates expression signatures implicating DNA damage repair, stemness, and Ras pathway activity as potential mediators of the phenotype. We identify specific molecular characteristics for investigation in patients within a poor prognosis subgroup of TNBC. Citation Format: Stover DG, Selfors LM, Winer EP, Partridge AH, Barry WT. Integrated transcriptional analysis of the triple negative 9proliferation paradox9: High proliferation, chemosensitivity, and poor prognosis [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 P1-07-05.

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 PD4-01: Acupuncture for chemotherapy-induced peripheral neuropathy in breast cancer, preliminary results of a pilot randomized controlled trial

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the major dose-limiting side effects in breast cancer patients, with up to 97% of patients receiving an adjuvant taxane experiencing this symptom in the months and years after breast cancer treatment. CIPN often leads to loss of physical function; difficulties in activities of daily living and decreased of quality of life (QOL). Few effective interventions have been developed to alleviate CIPN in this patient population. We conducted a pilot randomized controlled trial to assess the feasibility, safety and preliminary effect of an acupuncture intervention on CIPN in breast cancer survivors. METHODS: Patients with stage I-III breast cancer who were experiencing CIPN after the completion of a taxane-containing adjuvant chemotherapy regimen were enrolled and randomized 1:1 to immediate participation in an acupuncture intervention or to a delayed intervention control group. Participants randomized to the acupuncture arm received 18 sessions of a standardized acupuncture protocol over 8 weeks while the control group received a lower-dose acupuncture protocol consisting of 9 acupuncture sessions over 8 weeks, after the initial 8-week control period. Measures including the Patient Neurotoxicity Questionnaire (PNQ), Functional Assessment of Cancer Therapy Neurotoxicity subscale (FACT-NTX), and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Chemotherapy-induced Peripheral Neuropathy 20 (EORTC QLQ-CIPN20) were collected at baseline and at 8 weeks after enrollment. RESULTS: A total of 40 patients were enrolled; 20 were randomized to the immediate acupuncture group and 20 to control. All enrolled patients were female, median age was 54, median time between enrollment and completion of chemotherapy was 14.3 months, and 72.5% of participants were White. Thirty-two patients (84%) completed at least 80% of the required sessions. No serious acupuncture-related side effects were observed. Participants randomized to the acupuncture arm experienced improvements in the PNQ sensory score (p=0.02), FACT-NTX summary score (p=0.002) and EORTC QLQ-CIPN20 score (p=0.006), respectively equivalent to 40%, 36% and 53% improvement in CIPN symptoms, as compared to controls. CONCLUSIONS: Women with CIPN after adjuvant taxane therapy for early breast cancer experienced a significant and clinically meaningful improvement in neuropathy symptoms as a result of an 8-week acupuncture protocol. Given the prevalence of taxane-induced neuropathy in women treated for early breast cancer, acupuncture could significantly improve QOL and functional status of thousands of women treated for breast cancer every year. Larger studies are needed to confirm these findings and evaluate the impact of acupuncture on functional measures in women with CIPN. Citation Format: Lu W, Giobbie-Hurder A, Freedman R, Yung R, Lin N, Partridge A, Shockro L, Stecker K, O9Connor KA, Rosenthal DS, Ligibel JA. Acupuncture for chemotherapy-induced peripheral neuropathy in breast cancer, preliminary results of a pilot randomized controlled trial [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 PD4-01.

Abstract P1-10-18: Contraception use in young women with breast cancer

Background: Young women with breast cancer need highly effective contraception given the potential implications of unplanned pregnancy for optimal treatment, and the teratogenic risks. We sought to determine the contraceptive methods used by young women after diagnosis (dx) of breast cancer and factors associated with use of less effective methods or no contraceptive method, which confers a 6-90% annual risk of pregnancy in sexually active women in contrast to highly effective methods (risk Methods: As part of a randomized trial conducted in 54 sites to test an education and support intervention for young women with breast cancer and their oncologists, we surveyed women about their pre-dx, current, and planned contraceptive use, and about communication with their providers regarding contraception. Women enrolled within 3 months of dx; contraception items were included on 3- and 12-month post-enrollment surveys. Intrauterine device (IUD) use, tubal sterilization, hysterectomy or bilateral salpingo-oophorectomy (hyst/BSO) after dx, or male partner vasectomy were classified as highly effective methods; all other methods and non-use were categorized as less effective. We excluded women not at risk of pregnancy: hyst/BSO prior to dx, or no indication for contraception. We used logistic regression to explore factors associated with use of less effective methods. Results: Of 424 women who completed the 3-month post-enrollment survey, median age at dx was 39 (range 22-45). 312 women at risk of pregnancy were included in this analysis, including 291 reporting sexual activity with a male partner within the last 6 months, and 21 reporting no recent sexual activity but reporting use of birth control. 123 women (39%) used highly effective contraceptive methods prior to dx; after dx, 161 (52%) reported current use of or a plan to use a highly effective method. 19 women (6%) reported use of a hormonal birth control method since dx; 7 (2%) reported withdrawal as their only contraceptive method; 25 (8%) reported no contraception. 30% of women did not recall a discussion of avoiding pregnancy or need for contraception during treatment with their providers. In multivariable analyses (N=310), desire for additional biologic children (OR 7.54, 95% CI 3.88-14.66) and provider discussion of contraception and pregnancy (OR 2.13 95% CI 1.20-3.78) were associated with use of less effective contraception. Age, race/ethnicity, disease stage, and partner status were not significantly associated with use of less effective methods. Conclusion: About half of women who are at risk of pregnancy reported use or planned use of less effective contraceptive methods or no method of contraception following dx of breast cancer. Women with breast cancer and their providers may benefit from targeted education on contraceptive options and method effectiveness. Citation Format: Rosenberg SM, Dutton CR, Ligibel J, Barry W, Ruddy KJ, Sprunck-Harrild K, Emmons KM, Partridge AH. Contraception use in young women with breast cancer. [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 P1-10-18.

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 OT2-4-02: Young and strong: A randomized trial to evaluate a program for young women with breast cancer

Young women with newly diagnosed breast cancer face substantial challenges including higher risk of disease recurrence and likelihood of harboring a genetic mutation compared with older women. Many young women are also very concerned about their future fertility and this population often feels isolated from other breast cancer survivors due to their age and life stage. Some worry that their doctors are unsure of how to treat them. To address these issues, we developed a comprehensive program at our institution to coordinate and enhance the care, support, and education for young women with breast cancer. The Young and Strong study is a randomized clinical trial (RCT) to evaluate a virtual, exportable, scalable version of this program designed to improve the quality of care and the psychosocial well-being of this vulnerable population. The specific aims of this program are: 1) To develop, pilot, and refine an exportable and sustainable educational and support intervention for young women with breast cancer and their oncology providers (Young Women9s Intervention; YWI). 2) To determine the effect of the YWI compared to a contact-time control intervention focused on promoting physical activity (Physical Activity Intervention; PAI) on attention to fertility issues in a RCT: “Young and Strong”. We initially conducted 4 focus groups (n = 36) and 20 key informant interviews, and developed, piloted, and refined the YWI as well as the PAI. Based on this successful work, we launched the Young and Strong study in June 2012 as a cluster-randomized trial at a total of 54 sites (40 community and 14 academic sites across the United States). Randomization is 1:1 between sites, and stratified by practice type (community vs. academic). Each community site will enroll 5-10 participants, each academic site 15 participants. Total recruitment will be 410-610 pts. The primary objective is to evaluate whether YWI, as compared to PAI, is associated with greater attention to fertility issues, assessed via medical record review. In addition, participants will complete assessments at baseline, 3, 6, and 12 months that assess satisfaction with care, psychosocial well-being, physical activity and anthropomorphic changes. Young and Strong activated in June 2012 and all sites have been identified. As of 6/11/2013 the study has been initiated at 53 out of 54 sites, and total of 282 women have enrolled on the study. Eligibility Criteria: 1. Women age 18-45 years at diagnosis 2. Stage I-III invasive breast cancer without known recurrence or metastatic disease 3. Newly-diagnosed (within 3 months of initial diagnosis) 4. Have 1st appt. with a medical oncologist at participating site after the site opens to enrollment 5. Able to read and write in English For further information, contact Ann Partridge, MD, MPH at 888-814-3324. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr OT2-4-02.