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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 Although breast cancer often is perceived to be indolent in older women, breast cancer outcomes in the oldest patients are variable. In the current study, the authors examined breast cancer-specific death by age, stage, and disease subtype in a large, population-based cohort. Methods Using Surveillance, Epidemiology, and End Results data, a total of 486,118 women diagnosed with American Joint Committee on Cancer stage I to IV breast cancer between 2000 and 2012 were identified. Using a series of Fine and Gray regression models to account for competing risk, the authors examined the risk of breast cancer-specific death by age and stage (I-IV) for subcohorts with hormone receptor (HR)-positive, HR-negative, human epidermal growth factor receptor 2-positive, and triple-negative disease, adjusting for demographic and clinical variables. Results Overall, 18% of women were aged 65 to 74 years, 13% were aged 75 to 84 years, and 4% were aged ≥85 years. Regardless of stage of disease within the HR-positive and HR-negative cohorts, patients aged ≥75 years (vs those aged 55-64 years) experienced a higher adjusted hazard of breast cancer-specific death, which was particularly evident for those with early-stage, HR-positive disease (hazard ratio for those aged 75-84 years, 1.88 [95% confidence interval, 1.68-2.09] and hazard ratio for those aged ≥85 years, 3.59 [95% confidence interval, 3.12-4.13] [both for stage I disease]). In the cohorts with human epidermal growth factor receptor 2-positive and triple-negative disease, women aged ≥70 years had a consistently higher risk of breast cancer-specific death across disease stages (vs those aged 51-60 years), with the exception of stage IV triple-negative disease. Conclusions Older patients experience worse breast cancer outcomes, regardless of disease subtype and stage. With an increasing number of older patients anticipated to develop breast cancer in the future, addressing disparities for older patients must emerge as a clinical and research priority. Cancer 2018;124:2184-91. © 2018 American Cancer Society.

BACKGROUND Published studies have suggested that most patients with early stage breast cancer are willing, for modest survival benefits, to receive 6 months of adjuvant cyclophosphamide, methotrexate, and 5-fluorouracil, an older regimen that is used infrequently today. We examined preferences regarding the survival benefit needed to justify 6 months of a contemporary chemotherapy regimen. METHODS The Eastern Cooperative Oncology Group Protocol 5103 was a phase 3 trial that randomized breast cancer patients to receive standard adjuvant doxorubicin, cyclophosphamide, and paclitaxel with either bevacizumab or placebo. Serial surveys to assess quality of life were administered to patients enrolled between January 1, 2010, and June 8, 2010. Survival benefit needed to justify 6 months of chemotherapy by patients was collected at the 18-month assessment. A parallel survey was sent to physicians who had enrolled patients in the study. RESULTS Of 519 patients who had not withdrawn at a time point earlier than 18 months, 87.8% responded to this survey. A total of 175 physicians participated. We found considerable variation in patient preferences, particularly for modest survival benefits: for 2 months of benefit, 57% would consider 6 months of chemotherapy, whereas 96% of patients would consider 6 months of chemotherapy for 24 months. Race and education were associated with the choices. Physicians who responded were less likely to accept chemotherapy for modest benefit. CONCLUSIONS Among patients who received contemporary adjuvant chemotherapy in a randomized controlled trial, we found substantial variation in preferences regarding benefits that justified undergoing chemotherapy. Differences between patients' and physicians' choices were also apparent. Eliciting preferences regarding risks and benefits of adjuvant chemotherapy is critical. Cancer 2017;123:2821–28. © 2017 American Cancer Society.

BACKGROUND Exercise interventions improve fitness, functional capacity, and quality of life in patients with early-stage breast cancer, but to the authors' knowledge there are few data regarding the feasibility or potential benefits of exercise in women with metastatic breast cancer. METHODS Individuals with metastatic breast cancer were randomized 1:1 to a 16-week moderate-intensity exercise intervention or wait-list control group. Intervention goals included 150 minutes of moderate-intensity aerobic exercise per week. The baseline and 16-week evaluations included a modified Bruce Ramp treadmill test, 7-day Physical Activity Recall interview, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30) questionnaire. RESULTS A total of 101 participants were randomized (48 to the intervention group and 53 to the control group). The median age of the participants was 49 years, the median time since the diagnosis of metastatic breast cancer was 1.1 years, and approximately 42% of participants were undergoing chemotherapy at the time of enrollment. Study attrition was higher in the intervention arm (14 participants vs 8 participants; P = .15). Women randomized to the exercise intervention experienced a nonsignificant increase with regard to minutes of weekly exercise (62.4 minutes vs 46.0 minutes; P = .17) and physical functioning (EORTC QLQ C30: 4.79 vs 0.93 [P = .23] and Bruce Ramp Treadmill test: 0.61 minutes vs 0.37 minutes [P = .35]) compared with control participants. CONCLUSIONS Participation in an exercise intervention did not appear to result in significant improvements in physical functioning in a heterogeneous group of women living with advanced breast cancer. Given the significant benefits of exercise in women with early-stage breast cancer, more work is needed to explore alternative interventions to determine whether exercise could help women with metastatic disease live more fully with fewer symptoms from disease and treatment. Cancer 2016;122:1169–77. © 2016 American Cancer Society.

BACKGROUND Among patients with stage I breast cancer, there is significant uncertainty concerning the optimal threshold at which to consider chemotherapy, and when considered, there is controversy regarding whether to consider non-intensive versus intensive regimens. The authors examined the types and costs of adjuvant chemotherapy received among patients with stage I breast cancer. METHODS The current study was a prospective cohort study including patients with stage I breast cancer who were treated at a National Comprehensive Cancer Network center from 2000 through 2009. Stage was defined according to the version of the American Joint Committee on Cancer Staging Manual applicable at the time of diagnosis. Stratifying by human epidermal growth factor receptor 2 (HER2), the authors examined the percentage of patients receiving intensive versus non-intensive chemotherapy regimens and the factors associated with type of chemotherapy administered using multivariable logistic regression. Costs of the most common regimens were estimated. RESULTS Of 8907 patients, 33% received adjuvant chemotherapy. Among those individuals, there was an increase in the use of intensive chemotherapy within the last decade, from 31% in 2000 through 2005 to 63% in 2008 through 2009 (including an increase in the use of the combination of docetaxel, carboplatin, and trastuzumab) among patients with HER2-positive disease and from 15% in 2000 through 2005 to 41% in 2008 through 2009 among patients with HER2-negative disease (32% of patients with hormone receptor-positive and 59% of patients with triple-negative disease). Among patients treated with non-intensive regimens, there was an increase in the use of the combination of docetaxel and cyclophosphamide noted, with a decrease in the use of the doxorubicin and cyclophosphamide combination. The choice of regimen varied significantly by institution. The major drivers of cost variation were the incorporation of biologics (eg, trastuzumab) and growth factors, with significant variation even within non-intensive and intensive regimens. CONCLUSIONS Over time, there was an increase in use of intensive regimens among Stage I breast cancer, with striking institutional and cost variations. Cancer 2015;121:1937–1948. © 2015 American Cancer Society.

BACKGROUND Young women may experience delays in diagnosis of breast cancer, and these delays may contribute to poorer outcomes. METHODS In a prospective, multicenter cohort study, women recently diagnosed with breast cancer at age ≤40 years were surveyed regarding their initial signs or symptoms of cancer and delays in diagnosis. Self delay was defined as ≥90 days between the first sign or symptom and a patient's first visit to consult a health care provider. Care delay was defined as ≥90 days between that first visit and the diagnosis of breast cancer. In a medical record review, tumor characteristics were assessed, including disease stage. Univariate and multivariate models were used to assess for predictors of self delay, care delay, and advanced stage in the self-detected subset. RESULTS In 585 eligible participants, the first sign or symptom of cancer was a self-detected breast abnormality for 80%, a clinical breast examination abnormality for 6%, an imaging abnormality for 12%, and a systemic symptom for 1%. Among women with self-detected cancers, 17% reported a self delay, and 12% reported a care delay. Self delays were associated with poorer financial status (P = 0.01). Among young women with self-detected breast cancers, care delay was associated at trend level (P = .06) with higher stage in multivariate modeling. CONCLUSIONS Most young women detect their own breast cancers, and most do not experience long delays before diagnosis. Women with fewer financial resources are more likely to delay seeking medical attention for a self-detected breast abnormality. Cancer 2014;120:20–25. © 2013 American Cancer Society.

BACKGROUND The authors have previously reported 2 consecutive phase 2 trials in patients with early breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2) to assess the feasibility of incorporating anti-HER2 therapies into dose-dense (dd) chemotherapy regimens. The incidence of congestive heart failure (CHF) at a median follow-up of 2 years was 1.4% and 3.2%, respectively. METHODS In trial A, patients received dd doxorubicin and cyclophosphamide (AC)paclitaxel (T) (each given every 2 weeks) × 4 with trastuzumab (H) given × 1 year. In trial B, weekly T (weekly × 12) was substituted for ddT and lapatinib × 1 year was added. Herein, the authors report the longer-term incidence of CHF and distant disease-free survival (DDFS). RESULTS From January 2005 to May 2008, 165 patients enrolled (median age, 46 years, with a median left ventricular ejection fraction of 68% [range, 52%-81%]), 17%of whom had previous hypertension. With a median follow-up of 84 months (trial A) and 57 months (trial B), 1 additional patient developed CHF. Therefore, the cumulative incidence of CHF was 1.4% (95% confidence interval [95% CI], 1.36%-7.7%) for trial A and 4.2% (95% CI, 4.2%-10.4%) for trial B. The 5-year DDFS for trials A and B was 92% (95% CI, 83%-97%) and 89% (95% CI, 81%-94%), respectively. CONCLUSIONS Longer follow-up of these 2 studies has demonstrated that ddACTH only or with lapatinib is associated with a low risk of CHF and promising DDFS in patients with early breast cancer. Cancer 2013;119:3943–3951. © 2013 American Cancer Society.

BACKGROUND: Massachusetts law requires all residents to maintain a minimum level of health insurance, and rates of uninsurance in that state decreased from 6.4% in 2006 to 1.9% in 2010. The authors of this report assessed whether health insurance expansion was associated with use of mammography and earlier stage at breast cancer diagnosis. METHODS: By using a prereform/postreform design with a concurrent control (California), mammography rates in the last year were assessed using the Behavioral Risk Factor Surveillance System survey and the diagnosis of stage I (vs II/III/IV) breast cancers based on cancer registry data among women ages 41 to 64. Propensity score analyses were used to compare California women who were most similar to women in Massachusetts with Massachusetts women. RESULTS: Among propensity-weighted cohorts, adjusted mammography rates in Massachusetts were 69.2% in 2006, 69.5% in 2008, and 69.0% in 2010. In California, the rates were 59% in 2006, 60.3% in 2008, and 56.2% in 2010 (P = .89 for interaction by state for 2010 vs 2006). Among propensity-weighted cohorts, adjusted rates of diagnosis with stage I cancers were 52.2% in 2006, 53.5% in 2007, and 52.4% in 2008 in Massachusetts versus 46.4% in 2006, 46.3% in 2007, and 45.7% in 2008 in California (P = .58 for interaction by state for 2010 vs 2006). CONCLUSIONS: Health insurance reform in Massachusetts was not associated with increased rates of mammography or earlier stage at diagnosis compared with California, possibly because of insurance and mammography rates that already were high. Additional research is needed to assess the impact of insurance expansions in other populations, especially those with higher uninsurance rates. Cancer 2013. © 2012 American Cancer Society.

BACKGROUND: The objective of this study was to describe clinicopathologic features, patterns of recurrence, and survival according to breast cancer subtype with a focus on triple-negative tumors. METHODS: In total, 15,204 women were evaluated who presented to National Comprehensive Cancer Network centers with stage I through III breast cancer between January 2000 and December 2006. Tumors were classified as positive for estrogen receptor (ER) and/or progesterone receptor (PR) (hormone receptor [HR]-positive) and negative for human epidermal growth factor receptor 2 (HER2); positive for HER2 and any ER or PR status (HER2-positive); or negative for ER, PR, and HER2 (triple-negative). RESULTS: Subtype distribution was triple-negative in 17% of women (n = 2569), HER2-positive in 17% of women (n = 2602), and HR-positive/HER2-negative in 66% of women (n = 10,033). The triple-negative subtype was more frequent in African Americans compared with Caucasians (adjusted odds ratio, 1.98; P < .0001). Premenopausal women, but not postmenopausal women, with high body mass index had an increased likelihood of having the triple-negative subtype (P = .02). Women with triple-negative cancers were less likely to present on the basis of an abnormal screening mammogram (29% vs 48%; P < .0001) and were more likely to present with higher tumor classification, but they were less likely to have lymph node involvement. Relative to HR-positive/HER2-negative tumors, triple-negative tumors were associated with a greater risk of brain or lung metastases; and women with triple-negative tumors had worse breast cancer-specific and overall survival, even after adjusting for age, disease stage, race, tumor grade, and receipt of adjuvant chemotherapy (overall survival: adjusted hazard ratio, 2.72; 95% confidence interval, 2.39-3.10; P < .0001). The difference in the risk of death by subtype was most dramatic within the first 2 years after diagnosis (overall survival for 0-2 years: OR, 6.10; 95% confidence interval, 4.81-7.74). CONCLUSIONS: Triple-negative tumors were associated with unique risk factors and worse outcomes compared with HR-positive/HER2-negative tumors. Cancer 2012. © 2012 American Cancer Society.

Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer that constitutes between 12% and 15% of breast cancers.1 Although the biological characteristics and treatment options of DCIS have been the subject of growing research over the past several decades, only a small number of studies have examined the psychosocial sequelae of a DCIS diagnosis.2–6 In addition, no research has been conducted to identify socioeconomic subgroups of women who might be vulnerable to psychological morbidity after a DCIS diagnosis. Research on the psychosocial sequelae of a DCIS diagnosis is warranted for several reasons. First of all, DCIS is generally not life-threatening. When treated with standard therapy, the majority of cases will not result in local or systemic recurrence.1,7 Yet, similar to invasive breast cancer, the primary treatment for DCIS is surgery, with 30% of women undergoing mastectomy and 60% undergoing a breast-conserving procedure.1 Consequently, women with DCIS may experience many of the same psychosocial issues as women who are treated for invasive breast cancer, such as anxiety,8–10 depression, sexual problems, and negative body image.9 In fact, the limited research that has directly compared women with DCIS to women with invasive breast cancer has found no difference in their levels of psychological symptoms (ie, difficulty sleeping, anxiety, and depression),2 quality of life, and overall well-being.3 However, women with DCIS may experience fewer physical symptoms, better general health, and a less negative impact on their sex life and interpersonal relationships than women with invasive breast cancer.3 The word carcinoma and the surgical treatments for DCIS suggest a level of disease severity, and the distinction between invasive and noninvasive cancer can be confusing for many patients.4,5 In addition, women report being frustrated by the lack of available information about their DCIS.4,5 A shortage of information may leave women with DCIS unaware of their true breast cancer risk. For example, research suggests that women with DCIS do not differ from women with invasive breast cancer in their perceived risk of local or distant recurrence or distant metastases2 or of dying from their disease.3 Furthermore, between 54% and 61% of women perceived at least a moderate risk for disease recurrence,6,11 and 39% perceived at least a moderate risk for invasive cancer in the next 5 years.6 These risk perceptions are inaccurate, as true risk for local recurrence in the form of DCIS or invasive breast cancer after modern therapy ranges approximately 1% to 7%.12–14 Prior work from our group suggests that distress may contribute to inaccurate risk perceptions. For example, women with elevated DCIS-related intrusive or avoidant thoughts were more likely to overestimate their risk of metastasis, whereas women with elevated anxiety were more likely to overestimate their risk of a DCIS or invasive breast cancer recurrence and of developing invasive breast cancer in their lifetime.6 To effectively address the psychosocial needs of women with DCIS, it is important to consider that the incidence and prevalence of distress after DCIS may not be equal across all women, but instead may vary by socioeconomic status (SES). SES is inversely associated with psychological morbidity after an invasive cancer diagnosis.15–22 In addition, SES dictates access to important resources such as money, knowledge, and social connections/support that could be used to minimize the impact of a major health crisis such as a cancer diagnosis.23–29 Women with low SES may not have the same financial and psychosocial resources to cope with their DCIS; thus, this population may be vulnerable to anxiety and depression after their diagnosis. The extent to which SES affects distress after a DCIS diagnosis has not been previously addressed. The authors conducted a prospective longitudinal observational study to examine the psychosocial impact of a DCIS diagnosis.6 The current paper analyzes a subset of these data to examine whether SES was associated with anxiety and depression in these women. Because social support is inversely associated with distress across populations,30,31 and social support is positively associated with SES,24–28 this paper also explores whether the association between SES and distress was explained by differences in social support (mediation) and whether social support buffered against distress among women with low SES (moderation). We hypothesized that 1) women’s distress (anxiety and depression) would be inversely associated with their SES (education and financial status) at baseline and at the 9-month follow-up; 2) SES would predict a change in distress from baseline to the 9-month follow-up; and 3) social support would mediate and moderate the association between SES and anxiety and depression.

The Sixth Cambridge Conference on Endocrine and Targeted Manipulation of Breast Cancer was convened in Cambridge, Massachusetts on April 30 and May 1, 2007. The purpose of this multidisciplinary meeting of leaders in clinical and basic research and patient treatment was to assess the most recent data in the field, articulate current best practices, and identify the next steps to advance both patient care and research. Topics included a review of data from major recent and ongoing trials of endocrine treatment in patients with early breast cancer and from studies combining endocrine therapy with other treatment. The current status of breast cancer prevention efforts was examined. Preclinical models of response and resistance, initial efforts to profile tumor response and resistance during endocrine therapy in patients, and new developments in pharmacogenomics were also highlighted. In this article, a synopsis of the key issues discussed, conclusions, and recommendations are summarized; these are presented at greater length in the individual articles and accompanying Open Discussions that comprise the full conference proceedings. In the 2 years since the Fifth Conference, we have gained valuable follow-up data from key trials in early breast cancer, which have helped to clarify both the efficacy and safety and tolerability of the available strategies for endocrine therapy. Observations using endocrine agents in combination with other treatment have been similarly extended. More detailed analysis of preclinical models has improved our understanding of resistance to endocrine therapy, and efforts to explore these and other mechanisms in the clinic are now underway. All of this has and continues to contribute to a growing understanding of how to optimize the use of endocrine agents in both treating and preventing breast cancer.

BACKGROUND. Since 1992, pharmaceutical industry support has surpassed National Institutes of Health funding for clinical research in the United States. In this study, the authors sought to evaluate the impact of this shift in funding from public to private sponsors on the nature of published breast cancer clinical research. METHODS. All published breast cancer clinical trials from 2003, 1998, and 1993 were reviewed from 10 select English-language medical journals to evaluate pharmaceutical involvement over time and the association between sponsorship, trial design, and results. Clinical studies that reported disease-specific outcomes from medical therapy for breast cancer were eligible for analysis. Pharmaceutical involvement was defined as reported pharmaceutical industry funding, provision of drug, and/or authorship for each publication. RESULTS. In total, 140 eligible studies were identified, including 45 studies that were published in 1993, 39 studies that were published in 1998, and 56 studies that were published in 2003. Among those, 67 publications (48%) reported pharmaceutical industry involvement, 36 publications (26%) had at least ≥1 pharmaceutical industry author, And 100 publications (71%) were considered positive. Pharmaceutical involvement was identified in 44% of the studies published in 1993, in 38% of the studies published in 1998, and in 58% of the studies published in 2003. Pharmaceutical authorship was reported in 22% of the 1993 studies, in 21% of the 1998 studies, and in 34% of the 2003 studies. For studies that were published in 2003, those that reported pharmaceutical involvement were more likely to be positive (84% vs 54%; P = .02; Fisher exact test), to be single-arm studies (66% vs 33%; P = .03), and to evaluate metastatic disease (72% vs 46%; P = .06). CONCLUSIONS. Pharmaceutical involvement in published clinical breast cancer research may affect study design, focus, and results. Further research is warranted, including analysis of unpublished studies, to evaluate the impact of increasing pharmaceutical industry involvement on clinical research. Cancer 2007;109:. © 2007 American Cancer Society.

BACKGROUND. The optimal trastuzumab-based chemotherapy regimen for HER2-overexpressing, metastatic breast cancer is not known. The trastuzumab and vinorelbine or taxane (TRAVIOTA) study was a prospective, multicenter, randomized trial that was designed to compare these regimens. METHODS. Eligible patients had HER2-overexpressing, metastatic breast cancer and had received no prior chemotherapy for advanced disease. Patients were randomized 1:1 to receive either trastuzumab with weekly vinorelbine therapy or weekly taxane therapy (paclitaxel or docetaxel at the investigator's choice). Originally planned for 250 patients, the study was closed because of poor accrual with 81 evaluable patients, including 41 patients who received vinorelbine and 40 patients who received taxane. RESULTS. Response rates were 51% and 40% for the vinorelbine/trastuzumab arm and the taxane/trastuzumab arm, respectively (Fisher exact test; P = .37). The median time to disease progression was 8.5 months and 6.0 months for the vinorelbine- and taxane-based arms, respectively (log-rank test; P = .09). Treatment with either regimen generally was well tolerated, yielding comparable rates of neurologic and gastrointestinal toxicity. Vinorelbine-based treatment was associated with more anemia and neutropenia and with 2 episodes of cardiotoxicity. Taxane-based therapy was associated with more dermatologic toxicity, myalgias, and fluid retention. CONCLUSIONS. Both vinorelbine/trastuzumab and taxane/trastuzumab treatments were active as first-line therapy for HER2-positive, metastatic breast cancer and had comparable rates of efficacy and tolerability. The toxicities observed were the result of recognized side effects associated with each of the chemotherapy agents and schedules. These data can inform treatment decision making in this clinical setting. Cancer 2007. © 2007 American Cancer Society.

Exercise interventions improve fitness, functional capacity, and quality of life in patients with early-stage breast cancer, but to the authors' knowledge there are few data regarding the feasibility or potential benefits of exercise in women with metastatic breast cancer.Individuals with metastatic breast cancer were randomized 1:1 to a 16-week moderate-intensity exercise intervention or wait-list control group. Intervention goals included 150 minutes of moderate-intensity aerobic exercise per week. The baseline and 16-week evaluations included a modified Bruce Ramp treadmill test, 7-day Physical Activity Recall interview, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30) questionnaire.A total of 101 participants were randomized (48 to the intervention group and 53 to the control group). The median age of the participants was 49 years, the median time since the diagnosis of metastatic breast cancer was 1.1 years, and approximately 42% of participants were undergoing chemotherapy at the time of enrollment. Study attrition was higher in the intervention arm (14 participants vs 8 participants; P = .15). Women randomized to the exercise intervention experienced a nonsignificant increase with regard to minutes of weekly exercise (62.4 minutes vs 46.0 minutes; P = .17) and physical functioning (EORTC QLQ C30: 4.79 vs 0.93 [P = .23] and Bruce Ramp Treadmill test: 0.61 minutes vs 0.37 minutes [P = .35]) compared with control participants.Participation in an exercise intervention did not appear to result in significant improvements in physical functioning in a heterogeneous group of women living with advanced breast cancer. Given the significant benefits of exercise in women with early-stage breast cancer, more work is needed to explore alternative interventions to determine whether exercise could help women with metastatic disease live more fully with fewer symptoms from disease and treatment.

BACKGROUND The objective of this study was to compare the quality of life (QOL) after treatment among patients who had breast carcinoma with multiple positive lymph nodes. The patients were randomized to receive either high-dose chemotherapy with autologous stem cell support (HDC) or intermediate-dose chemotherapy (IDC) in the adjuvant setting. METHODS Two hundred forty-six patients with AJCC Stage IIA, IIB, or IIIA breast carcinoma who had ≥ 10 positive lymph nodes and who were participants in Cancer and Leukemia Group B (CALGB) 9082 were enrolled in this companion study, CALGB 9066. Patients were randomized to receive either high-dose cyclophosphamide, carmustine, and cisplatin (CPA/cDDP/BCNU) and autologous bone marrow transplantation (the HDC arm) or intermediate-dose CPA/cDDP/BCNU as consolidation to adjuvant chemotherapy (the IDC arm). QOL was assessed at baseline and at 3 months, 12 months, 24 months, and 36 months using the Functional Living Index-Cancer (FLIC), the Psychosocial Adjustment to Illness Scale (PAIS)-Self Report, and the McCorkle Symptom Distress Scale (SDS). RESULTS At the 3-month assessment, patients in the HDC arm demonstrated significant worsening of QOL compared with the IDC arm in terms of their physical well being (FLIC, P = 0.023), social functioning (FLIC, P = 0.026; PAIS, P < 0.0001), symptom distress (SDS, P = 0.0002), and total QOL scores (FLIC, P = 0.042). At 12 months, the differences in QOL scores between the HDC arm and the IDC arm had resolved. CONCLUSIONS Patients who received more intensive adjuvant therapy experienced transient declines in QOL. By 12 months after therapy, QOL was comparable between the 2 arms, regardless of therapy intensity, and many QOL areas were improved from baseline. Cancer 2005. © 2005 American Cancer Society.

Among patients with stage I breast cancer, there is significant uncertainty concerning the optimal threshold at which to consider chemotherapy, and when considered, there is controversy regarding whether to consider non-intensive versus intensive regimens. The authors examined the types and costs of adjuvant chemotherapy received among patients with stage I breast cancer.The current study was a prospective cohort study including patients with stage I breast cancer who were treated at a National Comprehensive Cancer Network center from 2000 through 2009. Stage was defined according to the version of the American Joint Committee on Cancer Staging Manual applicable at the time of diagnosis. Stratifying by human epidermal growth factor receptor 2 (HER2), the authors examined the percentage of patients receiving intensive versus non-intensive chemotherapy regimens and the factors associated with type of chemotherapy administered using multivariable logistic regression. Costs of the most common regimens were estimated.Of 8907 patients, 33% received adjuvant chemotherapy. Among those individuals, there was an increase in the use of intensive chemotherapy within the last decade, from 31% in 2000 through 2005 to 63% in 2008 through 2009 (including an increase in the use of the combination of docetaxel, carboplatin, and trastuzumab) among patients with HER2-positive disease and from 15% in 2000 through 2005 to 41% in 2008 through 2009 among patients with HER2-negative disease (32% of patients with hormone receptor-positive and 59% of patients with triple-negative disease). Among patients treated with non-intensive regimens, there was an increase in the use of the combination of docetaxel and cyclophosphamide noted, with a decrease in the use of the doxorubicin and cyclophosphamide combination. The choice of regimen varied significantly by institution. The major drivers of cost variation were the incorporation of biologics (eg, trastuzumab) and growth factors, with significant variation even within non-intensive and intensive regimens.Over time, there was an increase in use of intensive regimens among Stage I breast cancer, with striking institutional and cost variations.

BACKGROUND Megestrol acetate (MA) is a synthetic progestin with reported activity in both hormone-sensitive and hormone-refractory prostate carcinoma (HRPC). Based on limited data suggesting a possible dose-response effect, a trial was initiated to compare standard versus moderately high dose MA in HRPC. METHODS One hundred forty-nine men with hormone-refractory prostate carcinoma were randomized to receive oral MA either at 160 mg/day (low dose) or 640 mg/day (high dose). Patients were stratified by performance status and measurable versus evaluable disease. The primary end point was tumor response. Secondary end points were survival, quality-of-life measures, and prostate specific antigen (PSA) decline. RESULTS The median survival times of 11.2 months for patients who received the low dose and 12.1 months for patients who received the high dose therapy were not significantly different. Best response was equivalent in the 2 arms: 2 partial responses and 22 patients with stable disease for the 160 mg/day dose, and 1 partial response and 28 patients with stable disease for the 640 mg/day dose. A greater than 50% decline in PSA occurred in 13.8% and 8.8% of patients in the low and high dose treatment arms, respectively. There were no differences in the toxicity or quality-of-life outcomes between the two arms. Poorer performance status (2 vs. 0–1), greater than 5% weight loss, higher baseline PSA, and measurable disease all predicted shorter survival. CONCLUSIONS MA has limited activity in hormone-refractory prostate carcinoma, and there is no apparent dose-response correlation. Cancer 2000;88:825–34. © 2000 American Cancer Society.

BACKGROUND Axillary lymph node dissection is commonly performed as part of the primary management of breast carcinoma. Its value in patient management, however, has recently been questioned. Few studies exist that document long term complications. METHODS Four hundred thirty-two patients with Stage I or II breast carcinoma who were free of recurrence 2-5 years after surgery were identified. A cross-sectional survey was conducted to determine the prevalence of long term symptoms and complications as perceived by the patient, and patient and treatment factors that may have predicted complications were determined. Three hundred thirty of the 432 (76%) completed a mailed, self-administered questionnaire. In addition, the medical records of the 330 patients were reviewed. Patient and treatment factors were analyzed with logistic regression. RESULTS Numbness was reported by 35% of patients at the time of the survey. Pain was noted in 30%, arm swelling in 15%, and limitation of arm movement in 8%. Eight percent reported episodes of infection or inflammation at some point since the diagnosis of breast carcinoma. The majority of symptoms were mild and interfered minimally with daily activities. Younger age (P = 0.001) was associated with more frequent reporting of pain. Numbness was more common in younger patients (P = 0.004) as well as in those with a history of smoking (P = 0.012). There was a positive association of limitation of arm motion with adjuvant tamoxifen therapy (P = 0.016). Arm swelling was associated with both younger age (P = 0.004) and greater body surface area (P = 0.008). Radiation therapy was associated with a higher frequency of infection or inflammation in the arm and/or breast (P = 0.001). CONCLUSIONS Mild symptoms, especially pain and numbness, are common 2-5 years after axillary lymph node dissection. The frequency of inflammation or infection in patients treated with radiation to the breast or chest wall after an axillary lymph node dissection may be greater than previously appreciated. Severe complications or symptoms that have a major impact on daily activities are uncommon. These findings should help health care providers and their patients with breast carcinoma weigh the pros and cons of axillary lymph node dissection. Cancer 1998;83:1362-1368. © 1998 American Cancer Society.

The authors have previously reported 2 consecutive phase 2 trials in patients with early breast cancer that overexpresses human epidermal growth factor receptor 2 (HER2) to assess the feasibility of incorporating anti-HER2 therapies into dose-dense (dd) chemotherapy regimens. The incidence of congestive heart failure (CHF) at a median follow-up of 2 years was 1.4% and 3.2%, respectively.In trial A, patients received dd doxorubicin and cyclophosphamide (AC)→paclitaxel (T) (each given every 2 weeks) × 4 with trastuzumab (H) given × 1 year. In trial B, weekly T (weekly × 12) was substituted for ddT and lapatinib × 1 year was added. Herein, the authors report the longer-term incidence of CHF and distant disease-free survival (DDFS).From January 2005 to May 2008, 165 patients enrolled (median age, 46 years, with a median left ventricular ejection fraction of 68% [range, 52%-81%]), 17%of whom had previous hypertension. With a median follow-up of 84 months (trial A) and 57 months (trial B), 1 additional patient developed CHF. Therefore, the cumulative incidence of CHF was 1.4% (95% confidence interval [95% CI], 1.36%-7.7%) for trial A and 4.2% (95% CI, 4.2%-10.4%) for trial B. The 5-year DDFS for trials A and B was 92% (95% CI, 83%-97%) and 89% (95% CI, 81%-94%), respectively.Longer follow-up of these 2 studies has demonstrated that ddAC→TH only or with lapatinib is associated with a low risk of CHF and promising DDFS in patients with early breast cancer.

Young women may experience delays in diagnosis of breast cancer, and these delays may contribute to poorer outcomes.In a prospective, multicenter cohort study, women recently diagnosed with breast cancer at age ≤40 years were surveyed regarding their initial signs or symptoms of cancer and delays in diagnosis. Self delay was defined as ≥90 days between the first sign or symptom and a patient's first visit to consult a health care provider. Care delay was defined as ≥90 days between that first visit and the diagnosis of breast cancer. In a medical record review, tumor characteristics were assessed, including disease stage. Univariate and multivariate models were used to assess for predictors of self delay, care delay, and advanced stage in the self-detected subset.In 585 eligible participants, the first sign or symptom of cancer was a self-detected breast abnormality for 80%, a clinical breast examination abnormality for 6%, an imaging abnormality for 12%, and a systemic symptom for 1%. Among women with self-detected cancers, 17% reported a self delay, and 12% reported a care delay. Self delays were associated with poorer financial status (P = 0.01). Among young women with self-detected breast cancers, care delay was associated at trend level (P = .06) with higher stage in multivariate modeling.Most young women detect their own breast cancers, and most do not experience long delays before diagnosis. Women with fewer financial resources are more likely to delay seeking medical attention for a self-detected breast abnormality.

Massachusetts law requires all residents to maintain a minimum level of health insurance, and rates of uninsurance in that state decreased from 6.4% in 2006 to 1.9% in 2010. The authors of this report assessed whether health insurance expansion was associated with use of mammography and earlier stage at breast cancer diagnosis.By using a prereform/postreform design with a concurrent control (California), mammography rates in the last year were assessed using the Behavioral Risk Factor Surveillance System survey and the diagnosis of stage I (vs II/III/IV) breast cancers based on cancer registry data among women ages 41 to 64. Propensity score analyses were used to compare California women who were most similar to women in Massachusetts with Massachusetts women.Among propensity-weighted cohorts, adjusted mammography rates in Massachusetts were 69.2% in 2006, 69.5% in 2008, and 69.0% in 2010. In California, the rates were 59% in 2006, 60.3% in 2008, and 56.2% in 2010 (P = .89 for interaction by state for 2010 vs 2006). Among propensity-weighted cohorts, adjusted rates of diagnosis with stage I cancers were 52.2% in 2006, 53.5% in 2007, and 52.4% in 2008 in Massachusetts versus 46.4% in 2006, 46.3% in 2007, and 45.7% in 2008 in California (P = .58 for interaction by state for 2010 vs 2006).Health insurance reform in Massachusetts was not associated with increased rates of mammography or earlier stage at diagnosis compared with California, possibly because of insurance and mammography rates that already were high. Additional research is needed to assess the impact of insurance expansions in other populations, especially those with higher uninsurance rates.

Quality-of-life evaluation has gained increasing attention within the oncology community over the past 2 decades. The breadth of quality-of-life research in women with breast cancer has expanded substantially during this time. This paper reviews the status of quality-of-life research in women with breast cancer and explores several areas in which quality-of-life research can be of value. Descriptive quality-of-life studies in patients undergoing active treatment can identify the impact breast cancer treatment has on a patient's life. For patients who have completed treatment, research can detect areas of persistent distress. Quality-of-life assessment now is incorporated in many clinical trials. These data can provide a patient-rated assessment of treatment and complement the traditional endpoints in clinical trials. Examples of selected quality-of-life studies in patients with breast cancer are presented.

BACKGROUND: Few data are available on how race/ethnicity, insurance, and socioeconomic status (SES) interrelate to influence breast cancer treatment. The authors examined care for a national cohort of breast cancer patients to assess whether insurance and SES were associated with racial/ethnic differences in care. METHODS: The authors used multivariate logistic regression to assess the probability of definitive locoregional therapy, hormone receptor testing, and adjuvant systemic therapy among 662,117 white, black, and Hispanic women diagnosed with invasive breast cancer during 1998-2005 at National Cancer Data Base hospitals. In additional models, the authors included insurance and area-level SES to determine whether these variables were associated with observed racial/ethnic disparities. RESULTS: Most women were white (86%), 10% were black, and 4% were Hispanic. Most had private insurance (51%) or Medicare (41%). Among eligible patients, 80.0% (stage I/II) had definitive locoregional therapy, 98.5% (stage I-IV) had hormone receptor testing, and 53.1% and 50.2% (stage I-III) received adjuvant hormonal therapy and chemotherapy, respectively. After adjustment, black (vs white) women had less definitive locoregional therapy (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.88-0.94), hormonal therapy (OR, 0.90; 95% CI, 0.87-0.93), and chemotherapy (OR, 0.87; 95% CI, 0.84-0.91). Hispanic (vs white) women were also less likely to receive hormonal therapy. Hormone receptor testing did not differ by race/ethnicity. Racial disparities persisted despite adjusting for insurance and SES. CONCLUSIONS: The modest association between black (vs white) race and guideline-recommended breast cancer care was insensitive to adjustment for insurance and area-level SES. Further study is required to better understand disparities and to ensure receipt of care. Cancer 2011. © 2010 American Cancer Society.

The purpose of the current study was to characterize the outcomes of patients with metastatic triple-negative breast cancers, including the risk and clinical consequences of central nervous system (CNS) recurrence.Using pharmacy and pathology records, a study group of 116 patients who were treated for metastatic triple-negative breast cancer at Dana-Farber Cancer Institute between January 2000 and June 2006 was identified.The median survival from time of metastatic diagnosis was 13.3 months. Sixteen patients (14%) were diagnosed with CNS involvement at the time of initial metastatic diagnosis; overall, 46% of patients were diagnosed with CNS metastases before death. The median survival after a diagnosis of CNS metastasis was 4.9 months. The age-adjusted and race-adjusted rate of death for patients whose first presentation included a CNS metastasis was 3.4 times (95% confidence interval, 1.9-6.1 times) that of patients without a CNS lesion at the time of first metastatic presentation. Of the 53 patients who developed brain metastases, only 3 patients were judged to have stable or responsive systemic disease in the face of progressive CNS disease at the last follow-up before death.Triple-negative breast cancer is associated with poor survival after recurrence. CNS recurrence is common, but death as a direct consequence of CNS progression in the setting of controlled systemic disease is uncommon. Thus, it does not appear that the high rate of CNS involvement is because of a sanctuary effect, but rather is due to the lack of effective therapies in general for this aggressive subtype of breast cancer. New treatment strategies are needed.

BACKGROUND Emerging data suggest that treatment outcomes with aromatase inhibitors (AIs) and/or tamoxifen may differ for tumors that express both the estrogen receptor (ER) and the progesterone receptor (PR) (ER+/PR+) compared with those that lack PR expression (ER+/PR−). However, the optimal sequencing of AIs and tamoxifen as adjuvant therapy is not known and may differ for biologic subsets of cancers. METHODS Markov models were used to simulate disease-free survival (DFS) separately among postmenopausal women with ER+/PR+ cancers and women with ER+/PR− cancers. By using risk estimates reported from randomized clinical trials, treatment with 5 years of an AI alone with sequential treatment consisting of tamoxifen with crossover to an AI at 2 years was compared. RESULTS For women with ER+/PR+ cancers, sequential therapy with tamoxifen followed by crossover to an AI at 2 years yielded modest improvements in 10-year DFS estimates compared with planned AI monotherapy (84.3% vs. 82.2% and 68.8% vs. 64.8% for lymph node-negative and lymph node-positive patients, respectively). However, for women with ER+/PR− cancers, upfront treatment with an AI yielded improved outcomes with 10-year DFS rates of 90.5% and 80.1% for the lymph node-negative and node-positive groups, respectively, compared with 88.2% and 76.1%, respectively, for sequential treatment with tamoxifen followed by an AI. CONCLUSIONS Modeling estimates suggested that the optimal endocrine treatment strategy may differ based on the biologic features of breast cancer tumors. Patients with ER+/PR+ tumors achieved optimal 10-year DFS estimates with tamoxifen followed by a crossover to AI therapy, whereas patients with ER+/PR− tumors fared best when they initiated treatment with AI. Cancer 2006. © 2006 American Cancer Society.