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Background Breast cancer subtypes are associated with distinct metastatic patterns. Whether germline BRCA1 /BRCA2 mutation status is independently associated with central nervous system (CNS) relapse, controlling for tumor subtype, is unknown. Methods Patients who were treated at Dana‐Farber Cancer Institute and diagnosed with a first locoregional recurrence (LRR) or metastasis between 1981 and 2014 were identified using 2 institutional registries: 1) patients treated for recurrent breast cancer and 2) patients who underwent BRCA testing. The frequencies of LRR, sites of metastasis, and breast cancer‐specific survival from LRR or metastasis were calculated, and the factors associated with CNS recurrence were evaluated using multivariable logistic regression models. Results The final study cohort included 30 BRCA1 mutation carriers, 32 BRCA2 mutation carriers, and 270 noncarriers. Most BRCA1 carriers (73%) had triple‐negative breast cancer; whereas most BRCA2 carriers (72%) had hormone receptor‐positive tumors. BRCA1 carriers frequently experienced lung and distant lymph node metastasis, whereas BRCA2 carriers and noncarriers most often experienced bone metastasis. Although CNS disease occurred frequently in both BRCA1 and BRCA2 carriers (53% BRCA1, 50% BRCA2, 25% noncarriers; P, Germline BRCA1 or BRCA2 alterations are associated with a high frequency (≥50%) of brain metastases in patients with locoregionally recurrent or metastatic breast cancer. In multivariable analysis, only BRCA2 mutation (P = .006) was significantly associated with central nervous system metastasis when controlling for breast cancer subtype.

Background The objective of this study was to describe the perspective of patients with early breast cancer toward research biopsies. The authors hypothesized that more patients at academic sites than at community‐based sites would be willing to consider these procedures. Methods In total, 198 patients with early stage breast cancer were recruited from 3 academic centers (n = 102) and from 1 community oncology practice (n = 96). The primary objective was to compare the proportion of patients willing to consider donating excess tissue biospecimens from surgery, from a clinically indicated breast biopsy, or from a research purposes‐only biopsy (RPOB) between practice types. Results Most patients (93% at academic sites, 94% at the community oncology site) said they would consider donating excess tissue from surgery for research. One‐half of patients from academic or community sites would consider donating tissue from a clinically indicated breast biopsy. On univariate analysis, significantly fewer patients from academic sites would consider an RPOB (22% at academic sites, 42% at the community site; P = .003); however, this difference was no longer significant on multivariate analysis (P = .96). Longer transportation times and unfavorable prior experiences were associated with less willingness to consider an RPOB on multivariate analysis. Significantly fewer patients from academic sites (14%) than from the community site (35%) would consider a research biopsy in a clinical trial (P = .04). Contributing to scientific knowledge, return of results, and a personal request by their physician were the strongest factors influencing patients' willingness to undergo research biopsies. Conclusions The current results rejected the hypothesis that more patients with early breast cancer at academic sites would be willing to donate tissue biospecimens for research compared with those at community oncology sites. These findings identify modifiable factors to consider in biobanking studies and clinical trials., In this study of the willingness of patients with early stage breast cancer to consider biospecimen collection procedures for the purposes of research, most patients were willing to provide blood samples for research but were less likely to consider percutaneous breast biopsies. Longer travel time to the clinic and adverse experiences with prior biopsies, but not treatment center type (academic versus community‐based center), were associated with less willingness to consider research biopsies.

Background. Tissue from research biopsies provides access to insights into tumor biology. We aimed to determine medical oncologists’ (MOs’) attitudes toward research biopsies in patients with metastatic breast cancer (MBC). Materials and Methods. A total of 309 breast MOs from National Cancer Institute (NCI)-designated cancer centers were invited to complete a self-administered survey about their attitudes toward approaching patients for research purpose-only biopsies (RPOBs), performed as a standalone procedure, or additional biopsies, performed with a clinically indicated biopsy. The MOs were asked to predict what proportion of their MBC patients would consider undergoing research biopsies. Results. Of the 309 MOs, 221 (72%) responded. Of these 221 MOs, 30 were ineligible, leaving 191 eligible responders. Nearly all the MOs reported they were comfortable approaching patients regarding research biopsies of blood or skin. One fifth of MOs were uncomfortable approaching patients for RPOBs of the breast. One half of MOs were uncomfortable approaching patients for RPOBs of the liver. A significant variation was found in the perceptions by MOs of their patients’ willingness to undergo research biopsies. The factors associated with increased comfort in approaching patients for research biopsies included fewer years in practice, caring for patients who had undergone recent research biopsies, and the predicted willingness of patients to consent to biopsies. The risk of a biopsy and biopsy-related pain were the most common reasons for reluctance to refer patients for research biopsies. Conclusion. Significant variation exists, even at NCI centers, in the comfort level of MOs in approaching MBC patients for research biopsies. MOs’ attitudes toward research biopsies might be a modifiable factor in increasing tissue collection for research. Implications for Practice: Tissue-based research is critical in advancing our understanding of cancer biology, and obtaining tissue from a research biopsy provides an essential resource. This study demonstrates the variability of oncologists’ attitudes toward research biopsies and elicits factors associated with increased comfort levels with approaching patients for research biopsies. Biopsy risk and biopsy-related pain were commonly cited reasons not to refer patients for research biopsies. If the risk of a research biopsy is deemed sufficiently low enough to be acceptable, oncologists’ attitudes might be a potential target for education and change, which may assist in increasing the availability of tissue for cancer research.

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.

BACKGROUND: Young adults with cancer experience disruptions in their normal developmental trajectories and commonly experience psychological distress related to their diagnoses. Young women with metastatic breast cancer (MBC) are at particular risk of adverse mental health outcomes. OBJECTIVE: We sought to determine the prevalence of and factors associated with anxiety and depression symptoms in young women with newly diagnosed de novo MBC. METHODS: Fifty-four women with newly diagnosed de novo MBC were identified from an ongoing, prospective, multi-center cohort of women diagnosed with breast cancer at age

Background: Breast cancer is the second most common cancer associated with brain metastases. For some patients, central nervous system (CNS) progression is the primary clinical problem, and the optimal management of these patients remains a challenge. In this study we examined the differences in clinical characteristics, the features of CNS-directed therapy, and outcomes among breast cancer patients with brain metastases according to tumor subtype. Methods: A retrospective series of 214 breast cancer patients with brain metastases treated at the Dana-Farber Cancer Institute from 1999-2011 was identified. Tumor subtype was classified as hormone receptor (HR)+ (ER+/PR+/HER2-), triple negative (ER-/PR-/HER2-) or HER2+ (HER2+, any HR). Descriptive analysis was performed; Chi-square, Kruskal-Wallis, and Kaplan-Meier methods were used to compare clinical characteristics, CNS-directed therapy features, and outcomes between groups. Results: Median follow-up time since CNS progression was 8 months (0-117). Median age at CNS diagnosis was 52 years (30-82). Tumor subtype distribution was as following: 35% HR+, 36% HER2+, and 29% triple negative. Table 1 represents the clinical characteristics, CNS-directed therapy features, and outcomes according to tumor subtypes. More patients with triple negative disease (32%) had CNS involvement at presentation of metastatic disease. 8% of HER2+ patients had CNS as the only site of disease. A higher proportion of patients with HER2+ disease received more than one modality of CNS directed treatment as initial therapy. These patients also received more lines of CNS-directed therapy during the entire course of their disease. The median survival time after CNS progression differed by subtype; patients with HER2+ disease had the longest median survival times. Conclusions: Tumor subtype appears to impact clinical presentation, type and number of CNS-directed therapies, and survival among patients with breast cancer with brain metastases. Table 1 Tumor subtype HR+ (n = 74, 35%)HER2+ (n = 78, 36%)Triple negative (n = 62, 29%)P-valueBreakdown of treatment periods 0.2011999-200334%45%29% 2004-200628%17%31% 2007-201138%38%40% Clinical features at CNS disease presentationCNS disease at presentation of metastatic disease,%1522320.052Only site of metastatic disease,%181 Time from metastatic disease until CNS disease (median, min-max; months)16 (0-113)12 (0-65)6 (0-60) Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-11-09.

Background: In the era of molecularly targeted therapy, developing an understanding of the molecular basis of cancer is a principal or secondary goal of many research studies. For this reason, studies collecting tissue for research purposes are increasingly common. Understanding patients' attitudes towards research biopsies may lead to improvement in accrual to research biopsy studies. Methods: Patients with metastatic breast cancer from two academic and two community hospitals completed a self-administered paper survey consisting of 29 questions in clinic to evaluate their willingness to consider providing additional biopsies (additional biopsy performed with a clinically indicated biopsy) and research purposes only biopsies (RPOB) (research biopsy performed as a stand alone procedure). Results: 160 patients (n = 80 academic, n=80 community) completed the survey, with a response rate of 98%. As expected, demographic variables differed between sites, with patients from academic sites likely to be younger (p = 0.01), more educated (p = 0.002), employed (p = 0.01), have prior trial participation (P In univariate analyses of patients' willingness to have additional biopsies, patients in academic sites were more likely to agree to additional biopsies than those at community sites (RR = 1.2, 95% CI 1.0–1.5, p = 0.03). Statistically significant differences based on demographic characteristics such as age, education, marital status, prior trial participation, number of prior biopsies, and travel time were not observed. For RPOB, patients having had more prior biopsies were less likely to consider research biopsies (RR = 0.6, 95% CI 0.4–1.0, p = 0.03). The following variables did not reach statistical significance: type of practice, age, education, marital status, prior trial participation, and travel time. Patients' willingness in both academic and community sites to consider RPOB declined with more invasive biopsies. Although differences were observed, none were statistically significant between academic and community; skin (56%, 65%), bone marrow (30%, 27%), breast (43%, 49%) or liver (24%, 19%). Of the 13/160 (8%) patients who would not consider additional biopsies, the most common reasons cited included pain or discomfort (n = 8/13, 62%), risk of biopsy (n = 8/13, 62%) and anxiety related to the biopsy (n = 6/13, 46%). Of the 37/160 (23%) patients who would not consider RPOB, the most common reasons cited included pain or discomfort (n = 23/37, 62%), risk of biopsy (n = 15/37, 41%) and inconvenience of the procedure to the patient (n = 13/37, 35%). Conclusions: The majority of patients in this study indicated they would consider research biopsies, with a larger proportion willing to consider additional biopsies; patients seen at academic hospitals were more likely to consider additional biopsies compared to those seen at community hospitals. Breast cancer patients' willingness to undergo research biopsies may be higher than generally expected by clinicians and may not be the primary barrier to obtaining research biopsies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-16-04.

Background: HER2-positivity is a predictor of benefit from trastuzumab (TRZ), but fails to depict the observed interpatient variability in terms of treatment (tx) duration. In this study we described the relationship between clinicopathological features and TRZ tx duration. Methods: A retrospective consecutive series of 343 HER2+ breast cancer (BC) patients (pts) treated with TRZ at the Dana-Farber Cancer Institute from 1999–2008 was identified. 139 pts treated with 1st line TRZ-based tx were selected for analysis. Pts who received any non-TRZ prior tx for metastatic disease were excluded. TRZ tx duration was defined as time from start of 1st line therapy to the 1st day of 2nd line therapy or death. Central nervous system (CNS) progression with TRZ maintenance was not considered change of tx. Pts were divided equally into 3 groups based on the duration of 1st line tx distribution. Short-term responders (STR) were on the 1st line tx for 15m. An additional group of extremely LTR (ELTR) was defined as being in the 90th percentile of tx duration (>37m). Descriptive analysis was performed; fisher exact test, Kruskal-Wallis and logistic regression methods were used to compare groups. Results: Median follow-up time since metastatic diagnosis was 4 years (y) (range 0–11). Median age at diagnosis was 47y (22–83), 25% of stage I-III pts at diagnosis received adjuvant/neoadjuvant TRZ. The median disease free interval (DFI) was 20m (0–172), median number of metastatic sites was 2(1–5), 68% of pts had visceral disease. Median duration of 1st line tx was 10m (2–105). TRZ was given with CT in 86%, hormone tx in 6% and as monotherapy in 9%. 25% of pts developed CNS progression and continued tx. There were only small absolute differences for clinicopathological characteristics among STR, IR and LTR. ELTR had a median 1st line TRZ tx duration of 49m (37–105) and similar clinicopathological features to LTR. A higher proportion of LTR had hormone receptor (HR)-positive disease compared with STR, however no significant association between LTR and STR was found for HR status, DFI and visceral involvement. Conclusions: TRZ tx duration varies widely in the 1st-line advanced setting. No clinicopathological features were associated with TRZ tx duration. Our results suggest that despite CNS progression some pts continue to have long term benefit to TRZ tx. A major research priority is to identify molecular predictors of benefit and resistance to anti-HER2-based therapies. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P5-18-03.

Benefits of chemotherapy vary in patients with metastatic breast cancer (MBC). This article describes the impact of tumor subtype and the line of therapy on the duration of chemotherapy. Clinicopathologic characteristics were extracted from the medical records of 199 consecutive patients with MBC at Dana-Farber Cancer Institute and analyzed according to subtype. Tumor subtypes were classified as hormone receptor (HR)-positive, triple-negative (TNBC), or HER2-amplified breast cancer. Duration of chemotherapy of each line was defined as the start of a chemotherapy regimen to the start of the next line of therapy as a result of progression or toxicity. There were 96, 44, and 59 patients with HR(+), TNBC, and HER2-amplified breast cancer, respectively. Median age at MBC diagnosis was 53 years. Median overall survivals were 32 and 54 months for HER2-amplified disease, 36 months for HR(+) breast cancer, and 17 months for TNBC (P

Background The magnitude of benefit of trastuzumab for the treatment of advanced HER2-positive breast cancer varies widely. In this retrospective study, we investigated the clinicopathological features associated with prolonged first-line trastuzumab-based treatment duration. Patients and Methods A total of 164 patients diagnosed with advanced HER2-positive breast cancer and treated with first-line trastuzumab-based therapy from 1999 to 2009 were identified. Duration of treatment was classified according to tertiles. Different logistic regression models including age, disease-free interval, number of metastatic sites, visceral disease, hormone receptor, and adjuvant trastuzumab were fitted to investigate associations with benefit of prolonged trastuzumab-based therapies. The predictive value of each model was assessed using C-statistics. Results At a median follow-up of 5.8 years (range, 0.7-22.1 years), patients in the short-, intermediate-, and long-term treatment duration groups were given first-line trastuzumab-based therapy for 14 months, respectively. In the multivariate analysis, patients with long-term clinical benefit had a higher likelihood of having hormone receptor-positive tumors (odds ratio [OR] positive vs. negative = 2.39 [95% confidence interval (CI), 1.08-5.31]; P = .032); and a lower likelihood of having received adjuvant trastuzumab (OR adjuvant trastuzumab vs. no adjuvant trastuzumab = 0.30 [95% CI, 0.10-0.96]; P = .043]. C-statistics varied between 0.634 and 0.699. Conclusion Long-term benefit of trastuzumab-based therapy is associated with hormone receptor positivity and the absence of previous adjuvant trastuzumab. Nevertheless, clinicopathological features had a low predictive value for prolonged treatment duration. The validation of the current findings and the identification of molecular features associated the magnitude of trastuzumab benefit should be encouraged.