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The efficacy of pembrolizumab monotherapy versus chemotherapy increased with increasing programmed death ligand 1 (PD‐L1) expression, as quantified by combined positive score (CPS; PD‐L1 expression on both tumour cells and immune cells) in patients with previously treated metastatic triple‐negative breast cancer (mTNBC) in the phase 3 KEYNOTE‐119 study. This exploratory analysis was conducted to determine whether the expression of PD‐L1 on tumour cells contributes to the predictive value of PD‐L1 CPS in mTNBC. PD‐L1 expression in tumour samples was assessed using PD‐L1 IHC 22C3 pharmDx and quantified using both CPS and tumour proportion score (TPS; PD‐L1 expression on tumour cells alone). Calculated immune cell density (CID) was defined as CPS minus TPS. The ability of each scoring method (CPS, TPS, and CID) to predict clinical outcomes with pembrolizumab was evaluated. With pembrolizumab, the area under the receiver operating characteristic curve was 0.69 (95% CI = 0.58–0.80) for CPS, 0.55 (95% CI = 0.46–0.64) for TPS, and 0.67 (95% CI = 0.56–0.77) for CID. After correction for cutoff prevalence, CPS performed as well as, if not better than, CID with respect to predicting objective response rate, progression‐free survival, and overall survival. Data from this exploratory analysis suggest that, although PD‐L1 expression on immune cells alone is predictive of response to programmed death 1 blockade in mTNBC, adding tumour PD‐L1 expression assessment (i.e. CPS, which combines immune cell and tumour cell PD‐L1 expression) may improve prediction. PD‐L1 CPS thus remains an effective and broadly applicable uniform scoring system for enriching response to programmed death 1 blockade with pembrolizumab in mTNBC as well as other tumour types. [ABSTRACT FROM AUTHOR]

Background: The optimal treatment strategy for patients with small human epidermal growth factor receptor 2 (HER2)‐positive tumors is based on nodal status. The authors' objective was to evaluate pathologic nodal disease (pathologic lymph node‐positive [pN‐positive] and pathologic lymph node‐positive after preoperative systemic therapy [ypN‐positive]) rates in patients who had clinical T1–T2 (cT1–cT2)N0M0, HER2‐positive breast cancer treated with upfront surgery or neoadjuvant chemotherapy (NAC). Methods: Two databases were queried for patients who had cT1–cT2N0M0, HER2‐positive breast cancer: (1) the Dana‐Farber Brigham Cancer Center (DF/BCC) from February 2015 to October 2020 and (2) the Hospital Clinic of Barcelona and the Hospital Clinico of Valencia (HCB/HCV) from January 2012 to September 2021. The pN‐positive/ypN‐positive and axillary lymph node dissection (ALND) rates were compared between patients who underwent upfront surgery versus those who received NAC. Results: Among 579 patients from the DF/BCC database, 368 underwent upfront surgery, and 211 received NAC; the rates of nodal positivity were 19.8% and 12.8%, respectively (p =.021). The pN‐positive rates increased by tumor size (p <.001), reaching 25% for those with cT1c tumors. The ypN‐positive rates did not correlate with tumor size. NAC was associated with decreased nodal positivity (odds ratio, 0.411; 95% confidence interval, 0.202–0.838), but the ALND rates were similar (22 of 368 patients [6.0%] who underwent upfront surgery vs. 18 of 211 patients [8.5%] who received NAC; p =.173). Among 292 patients from the HCB/HCV database, 119 underwent upfront surgery, and 173 received NAC; the rates of nodal positivity were 21% and 10.4%, respectively (p =.012). The pN‐positive rates increased with tumor size (p =.011). The ALND rates were equivalent by treatment strategy (23 of 119 patients [19.3%] who underwent upfront surgery vs. 24 of 173 patients [13.9%] who received NAC; p =.213). Conclusions: Among patients who had cT1–cT2N0M0, HER2‐positive breast cancer, approximately 20% who underwent upfront surgery were pN‐positive, and the rate reached 25% for those with cT1c tumors. Given the opportunity for tailored therapy among lymph node‐positive, HER2‐positive patients, these data provide rationale for future analyses investigating the utility of routine axillary imaging in patients with HER2‐positive breast cancer. Data from patients with clinical T1–T2N0, human epidermal growth factor receptor 2‐positive breast cancer who either underwent upfront surgery or received neoadjuvant chemotherapy were extracted from two institutional databases. Nodal positivity rates were >20% at upfront surgery; neoadjuvant chemotherapy decreased nodal positivity rates, but axillary lymph node dissection rates were equivalent. [ABSTRACT FROM AUTHOR]

Background: Neoadjuvant chemotherapy (NAC) is standard for many females with breast cancer (FBC). The efficacy of NAC in male breast cancer (MaBC) is unclear. The aim of this study was to compare proportions of pathologic complete response (pCR) between MaBC and FBC by tumor subtype (TS).Methods: MaBC and FBC treated with NAC between 2010 and 2016, with known TS, were evaluated from the National Cancer Database. Proportions of pCR (ypT0/Tis ypN0) were compared between sexes within TS by Fisher test. Multivariable logistic regression assessed the independent association of sex with pCR. Overall survival (OS) was estimated by Kaplan-Meier.Results: A total of 385 MaBC and 68,065 FBC were included. Median time from initiation of NAC to surgery was 143 days in MaBC and 148 days in FBC. Proportions of pCR in MaBC and FBC by TS were: hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-): 4.9% vs 9.7%, p = .01; HR+/HER2+: 16.1% vs 33.6%, p < .001; HR-/HER2+: 44.0% vs 53.2%, p = .42; and HR-/HER2-: 21.4% vs 32.1%, p = .18, respectively. FBC had twice the odds of pCR than MaBC (adjusted odds ratio, 2.0; 95% CI, 1.5-2.8; p < .001). Five-year OS for MaBC with pCR vs not was 90% vs 64.7%; p = .02. Five-year OS for FBC with pCR vs not was 91.9% vs 75.3%; p < .01.Conclusions: Proportions and odds of pCR to NAC were numerically lower in MaBC compared with FBC for each TS and statistically significant for HR+/HER2- and HR+/HER2+. The independent association of sex with pCR was confirmed in multivariable analysis. pCR is prognostic in both MaBC and FBC. [ABSTRACT FROM AUTHOR]

The Breast Cancer Weight Loss (BWEL) trial is a randomized controlled trial designed to determine whether weight loss after a breast cancer diagnosis can reduce the risk of cancer recurrence in women with overweight or obesity. The BWEL trial will compare the efficacy of a telephone-based weight-loss intervention plus health education materials versus health education materials alone on invasive disease-free survival in 3,181 women with stage II or III breast cancer and BMI > 27 kg/m2 . This report provides a detailed description of the goals and methods of the lifestyle intervention and the evidence supporting the intervention used in the BWEL trial. The intervention's primary goal for participants is to achieve and maintain a weight loss ≥ 10% of baseline weight through increased physical activity and caloric restriction. The evidence supporting the diet, physical activity, and behavioral components of this telephone-based weight-loss intervention, as well as strategies to promote participant engagement and retention, is described. The intervention is provided through 42 sessions delivered by trained health coaches over a 2-year period. If the BWEL lifestyle intervention is successful in improving cancer outcomes, then weight loss will be incorporated into the care of thousands of breast cancer patients. [ABSTRACT FROM AUTHOR]

Background: Many patients with myelodysplastic syndromes (MDS) receive red cell transfusions to relieve symptoms associated with anemia, with transfusions triggered by hemoglobin level. It is not known if patients' quality of life (QOL) improves after transfusion, nor if peri‐transfusion QOL assessment (PTQA) can guide future transfusion decisions. Study Design and Methods: We conducted a prospective pilot study of adults with MDS at three centers. Participants, who had to have hemoglobin ≥7.5, completed an MDS‐specific measure of QOL (the Quality of Life in Myelodysplasia Scale, [QUALMS]) 1 day before and 7 days after red cell transfusion. A report was sent to each patient and provider before the next transfusion opportunity, indicating whether there were clinically significant changes in QOL. We assessed the proportion of patients experiencing changes in QOL, and with a follow‐up questionnaire, whether they perceived their PTQA data were used for future transfusion decisions. Results: From 2018 to 2020, 62 patients enrolled (mean age 73 years) and 37 completed both pre‐ and post‐transfusion QOL assessments. Of these, 35% experienced a clinically significant increase in QUALMS score 7 days after transfusion; 46% no change; and 19% a decrease. Among those completing the follow‐up questionnaire, 23% reported that PTQA results were discussed by their provider when considering repeat transfusion. Conclusions: These data suggest PTQA is feasible for patients with MDS. Moreover, while helpful for some, for many others, red cell transfusion may not achieve its intended goal of improving QOL. PTQA offers a strategy to inform shared decision‐making regarding red cell transfusion. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Chemotherapy‐induced peripheral neuropathy (henceforth, neuropathy) is often dose limiting and is generally managed by empirical dose modifications. We aimed to (1) identify an early time point that is predictive of future neuropathy using a patient‐reported outcome and (2) propose a dose‐adjustment algorithm based on simulated data to manage neuropathy. In previous work, a dose‐neuropathy model was developed using dosing and patient‐reported outcome data from Cancer and Leukemia Group B 40502 (Alliance), a randomized phase III trial of paclitaxel, nanoparticle albumin–bound paclitaxel or ixabepilone as first‐line chemotherapy for locally recurrent or metastatic breast cancer. In the current work, an early time point that is predictive of the future severity of neuropathy was identified based on predictive accuracy of the model. Using the early data and model parameters, simulations were conducted to propose a dose‐adjustment algorithm for the prospective management of neuropathy in individual patients. The end of the first 3 cycles (12 weeks) was identified as the early time point based on a predictive accuracy of 75% for the neuropathy score after 6 cycles. For paclitaxel, nanoparticle albumin–bound paclitaxel, and ixabepilone, simulations with the proposed dose‐adjustment algorithm resulted in 61%, 48%, and 35% fewer patients, respectively, with neuropathy score ≥8 after 6 cycles compared to no dose adjustment. We conclude that early patient‐reported outcome data on neuropathy can be used to guide dose adjustments in individual patients that reduce the severity of future neuropathy. Prospective validation of this approach should be undertaken in future studies. [ABSTRACT FROM AUTHOR]

Mutations in the E3 ubiquitin ligase CBL, found in several myeloid neoplasms, lead to decreased ubiquitin ligase activity. In murine systems, these mutations are associated with cytokine‐independent proliferation, thought to result from the activation of hematopoietic growth receptors, including FLT3 and KIT. Using cell lines and primary patient cells, we compared the activity of a panel of FLT3 inhibitors currently being used or tested in AML patients and also evaluated the effects of inhibition of the non‐receptor tyrosine kinase, SYK. We show that FLT3 inhibitors ranging from promiscuous to highly targeted are potent inhibitors of growth of leukaemia cells expressing mutant CBL in vitro, and we demonstrate in vivo efficacy of midostaurin using mouse models of mutant CBL. Potentiation of effects of targeted FLT3 inhibition by SYK inhibition has been demonstrated in models of mutant FLT3‐positive AML and AML characterized by hyperactivated SYK. Here, we show that targeted SYK inhibition similarly enhances the effects of midostaurin and other FLT3 inhibitors against mutant CBL‐positive leukaemia. Taken together, our results support the notion that mutant CBL‐expressing myeloid leukaemias are highly sensitive to available FLT3 inhibitors and that this effect can be significantly augmented by optimum inhibition of SYK kinase. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Plasmablastic lymphoma ( PBL) is a rare and aggressive CD20-negative lymphoma. Despite improvements of the biology behind PBL, it still represents a challenge from the diagnostic and therapeutic perspectives for pathologists and clinicians. PBL is characterized by high rates of relapse and short median survival with standard approaches. Here, we report the use of the combination of bortezomib and infusional etoposide, prednisone, vincristine, cyclophosphamide and doxorubicin (V- EPOCH) in three patients with PBL; two were HIV-positive and one was HIV-negative. All three patients obtained a durable complete response to V- EPOCH with survival times of 24, 18 and 12 months respectively. [ABSTRACT FROM AUTHOR]

Preventing chemotherapy-induced thrombocytopenia could avoid chemotherapy dose reductions and delays. The safety and maximum tolerated dose of eltrombopag, an oral thrombopoietin receptor agonist, with gemcitabine-based therapy was evaluated. Patients with advanced solid tumors and platelets ≤300 × 109/L receiving gemcitabine plus cisplatin or carboplatin (Group A) or gemcitabine monotherapy (Group B) were randomized 3:1 to receive eltrombopag or placebo at a starting dose of 100 mg daily administered on days −5 to −1 and days 2-6 starting from cycle 2 of treatment. Nineteen patients (Group A, n = 9; Group B, n = 10) received eltrombopag 100 mg and seven (Group A, n = 3; Group B, n = 4) received matching placebo. Nine eltrombopag patients in Group A and eight in Group B had 38 and 54 occurrences of platelet counts ≥400 × 109/L, respectively. Mean platelet nadirs across cycles 2-6 were 115 × 109/L and 143 × 109/L for eltrombopag-treated patients versus 53 × 109/L and 103 × 109/L for placebo-treated patients in Groups A and B, respectively. No dose-limiting toxicities were reported for eltrombopag; however, due to several occurrences of thrombocytosis, a decision was made not to dose-escalate eltrombopag to >100 mg daily. In Groups A and B, 14% of eltrombopag versus 50% of placebo patients required chemotherapy dose reductions and/or delays for any reason across cycles 3-6. Eltrombopag 100 mg once daily administered 5 days before and after day 1 of chemotherapy was well tolerated with an acceptable safety profile, and will be further tested in a phase II trial. Fewer patients receiving eltrombopag required chemotherapy dose delays and/or reductions compared with those receiving placebo. [ABSTRACT FROM AUTHOR]

Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive ( HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2-negative operable breast cancer received capecitabine, 2000 mg/m2 daily in divided doses for 14 days, followed by a 7-day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response ( pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller-Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase ( TYMP), thymidylate synthase ( TYMS), dihydropyrimidine dehydrogenase ( DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well-tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 ddAC→TH 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. [ABSTRACT FROM AUTHOR]

Objective To examine whether hospitals where patients obtain care explain racial/ethnic differences in treatment delay. Data Source Surveillance, Epidemiology, and End Results data linked with Medicare claims. Study Design We examined delays in adjuvant chemotherapy or radiation for women diagnosed with stage I-III breast cancer during 1992-2007. We used multivariable logistic regression to assess the probability of delay by race/ethnicity and included hospital fixed effects to assess whether hospitals explained disparities. Principal Findings Among 54,592 women, black (11.9 percent) and Hispanic (9.9 percent) women had more delays than whites (7.8 percent, p < .0001). After adjustment, black (vs. white) women had higher odds of delay (odds ratio = 1.25, 95 percent confidence interval = 1.10-1.42), attenuated somewhat by including hospital fixed effects ( OR = 1.17, 95 percent CI = 1.02-1.33). Conclusions Hospitals are the important contributors to racial disparities in treatment delay. [ABSTRACT FROM AUTHOR]

Objective To assess body image concerns among young women following a breast cancer diagnosis. Methods A total of 419 women with recently diagnosed stage 0-III breast cancer were surveyed following enrollment as part of a prospective cohort study of women age 40 or younger at diagnosis. Body image was assessed using three items from the psycho-social scale of the Cancer Rehabilitation Evaluation System (CARES). CARES scores range from 0 to 4, with higher scores indicative of greater image concerns. Mean CARES scores were calculated and compared between treatment groups using t-tests and analysis of variance. Multiple linear regression models were fit to evaluate the relationship between physical and psychological factors and body image. Results Mean time from diagnosis to completion of the baseline survey was 5.2 months. The mean CARES score for all women was 1.28. Mean CARES scores in the mastectomy-only group (1.87) and in the mastectomy with reconstruction group (1.52) were significantly higher ( p < 0.0001) compared with the scores in the lumpectomy group (0.85), indicating that radical surgery was associated with more body image concerns. Radiation ( p = 0.01), anxiety ( p = 0.0001), depression ( p < 0.0001), fatigue ( p = 0.04), musculoskeletal pain symptoms ( p < 0.0001), weight gain ( p = 0.01), and weight loss ( p = 0.02), in addition to surgery type ( p < 0.0001), were all associated with more body image concerns in the multi-variable analysis. Conclusion This analysis highlights the impact of treatment, along with physical and psychological factors, on body image early in the survivorship period. Our findings provide targets for potential future intervention and may aid young women in the surgical decision-making process. Copyright © 2012 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The article presents information which whether insurance and socioeconomic status (SES) were related to racial or ethnic differences in care. The feasibility of definitive iocoregional therapy, hormone receptor testing, and adjuvant systemic therapy among white, black, and Hispanic women diagnosed with invasive breast cancer from 1998 to 2005 at National Cancer Data Base hospitals was likewise determined. It discusses the findings of the study. It concludes that additional studies are needed to better understand disparities and to ensure receipt of care.

The article presents a study that evaluates the relationship between the socioeconomic status (SES) and distress particularly anxiety and depression in women diagnosed with ductal carcinoma in situ (DCIS). The study is undertaken on 487 women diagnosed with DCIS. Results of the study show that financial status inversely affects anxiety and depression. It concludes that women having medium or low SES were likely to report an increase anxiety and depression after being diagnosed with DCIS.

Background: 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.Methods: 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.Results: 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.Conclusions: 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. [ABSTRACT FROM AUTHOR]

Objectives: The Survivor's Health and Reaction study used a quality-of-life model adapted for cancer survivors by Dow and colleagues to identify factors related to global health-related quality of life (HRQL) and to document the prevalence of problems and health-oriented behaviors in a follow-up study of breast cancer patients who participated in CALGB 8541. Methods: A total of 245 survivors (78% of those invited) who were 9.4–16.5 years post-diagnosis completed surveys that inquired about current HRQL, economic, spiritual, physical and psychosocial concerns, and health-oriented behaviors (e.g. smoking, exercise, and supplement use). A regression model was developed to examine factors related to global HRQL across all domains. Results: The regression model revealed that decreased energy levels (odds ratio (OR)=1.05, 95% confidence interval (CI): 1.03, 1.07), having heart disease (OR=5.01, 95% CI: 1.39, 18.1), having two or more co-morbidities (OR=2.39, 95% CI: 1.10, 5.19), and lower social support (OR=1.03, 95% CI: 1.02, 1.05) were associated with lower global HRQL. Factors related to psychological, spiritual, and economic domains were not predictive of global HRQL. Regarding lifestyle changes, some women reported engaging in health-oriented behaviors since their cancer diagnosis, such as improving eating habits (54%), increasing exercise (32%), and reducing/quitting smoking (20%). The most prevalent problems reported by women at follow-up were menopausal symptoms (64%), such as hot flashes and vaginal dryness, osteoporosis (25%), and lymphedema (23%). Conclusion: Suggestions are provided to target interventions, such as provider-based strategies, in order to improve HRQL in long-term breast cancer survivors. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Five years of adjuvant therapy with tamoxifen was considered the gold-standard treatment for postmenopausal women with estrogen receptor-positive breast cancer for many years. Data from a core group of clinical trials investigating the safety and efficacy of aromatase inhibitors (AIs) have challenged this perception. These studies were designed to evaluate the safety and efficacy of AIs in the following clinical settings: 1) as initial adjuvant therapy (the Arimidex, Tamoxifen, Alone or in Combination trial, Breast International Group Trial 1-98), 2) in a "switched setting" after 2 to 3 years of treatment with tamoxifen (Arimidex-Nolvadex 95, the Austrian Breast and Colorectal Cancer Study Group 8 [ABCSG 8] trial, the Italian Tamoxifen Anastrozole study, the Intergroup Exemestane Study), and 3) in extended settings (National Cancer Institute of Canada Trial MA.17, ABCSG 6a, National Surgical Adjuvant Breast and Bowel Project 33). The efficacy data from these studies suggested that AIs have added substantial benefit in terms of disease outcome. AIs were tolerated well, and patients who received them experienced fewer thrombolic events and less endometrial cancer, hot flashes, night sweats, and vaginal bleeding compared with patients who receive tamoxifen. However, patients who received tamoxifen had less skeletal events and accelerated bone resorption compared with women who received AIs. AIs should be considered when planning a patient's endocrine therapy, taking into account the differences in tolerability and end-organ effects of the classes of endocrine therapy. Outstanding issues to optimize AI therapy include identifying the optimal duration, agent, and patients for these therapies. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The study's objective was to test whether there were signfiicant differences in adjustment between younger and older breast and endometrial cancer survivors. Methods: Two hundred and fifty-two breast and endometrial cancer survivors participated in this study, ranging in age from either 18 to 55 years old or 65 years old or older. Survivors were interviewed by telephone at study entry and 12 months, using a battery of measures to assess their adjustment, physical functioning, and treatment-related physical problems. Results: With an average of 3.7 years since treatment completion, almost all survivors reported good adjustment to having had cancer. While most differences in psychosocial adjustment between groups were small, younger survivors reported significantly worse adaptation than older survivors, as measured by the Hospital Anxiety and Depression Scale (HADS, p<0.0001), Appearance-Orientation Scale (AOS, body image; p=0.02), Fear of Recurrence (p<0.0001), Distress about Long-term Treatment-Related Cancer Problems (p=0.01), and Number of Sexual Problems Attributed to Cancer (p<0.0001). Conclusion: Survivors reported few cancer-related problems with only a small subset reporting problems in adjustment. Although differences were small, younger cancer survivors reported significantly worse adaptation than older survivors. Much of the adaptation to having had cancer may have already occurred in long-term survivors. Copyright © 2007 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article presents a study which described the vinorelbine/trastuzumab and taxane/trastuzumab treatments for HER2-positive, metastatic breast cancer. The study included eligible patients which had HER2-overexpressing, metastatic breast cancer and had received no prior chemotherapy for advanced disease. The study found that response rates were 51% and 40% for the vinorelbine/trastuzumab arm and the taxane/trastuzumab arm, respectively.

Background: The study's objective was to evaluate the reliability and validity of the Cancer-Related Communication Problems within Couples Scale (CRCP), a measure to assess whether patients and their partners have difficulty talking about cancer with each other. Methods: The CRCP Scale included 18 items concerning open communication/emotional support, treatment-specific issues, self-protection, and protective buffering. Patients and partners responded through the American Cancer Society's website and mailed questionnaires through Y-ME. The CRCP's validity was tested using the Hospital Anxiety and Depression Scale (HADS) and the Dyadic Adjustment Scale (DAS, marital relationship). Results: 189 female patients and 135 male partners participated in the survey. Three items were deleted based on lack of clarity or an item not being applicable to many respondents, resulting in a 15 item scale. The number of CRCP problems' internal consistency in the 15 item scale was good for both patients and partners (alpha coefficient=0.87, 0.81, respectively). The number of patients' CRCP problems correlated with the DAS (p<0.0001), and the number of partners' CRCP problems correlated with the HADS (p<0.0001) and the DAS (p<0.0001). Conclusion: Analyses supported the CRCP Scale's reliability and validity for female cancer patients and male partners. Copyright © 2005 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Women with a strong family history of breast and/or ovarian cancer can now have genetic testing, that may identify mutations associated with increased cancer predisposition. Within the context of a clinical trial evaluating printed educational materials, we examined motivation, satisfaction, coping, and perceptions of genetic counseling and testing among 159 women who underwent pretest counseling and made a testing decision. Ninety-six percent of the participants elected to have BRCA1/2 testing. When making a decision about genetic testing, study participants were concerned less about the potential negative effects that could result from testing than the potential benefits. After counseling, participants said that they felt better able to make decisions that were right for them and that their questions and concerns were adequately addressed during the session. Ninety-five percent of the women were satisfied with their test decision. Participants used a range of strategies to cope with thoughts and feelings about cancer and/or genetic testing immediately following test decision. Results suggest that the genetic counseling session helped women make decisions about testing for BRCA1 and BRCA2, even in the setting of a trial in which all women also received detailed educational materials. Further, the results indicate that future research focusing on perceptions of risks and benefits of testing and of coping strategies immediately following test decision may be warranted. [ABSTRACT FROM AUTHOR]

Background: Over the past decade, high dose chemotherapy with autologous bone marrow (HDC-ABMT) support has been used increasingly in the treatment of patients with breast cancer. In evaluating the results of HDC-ABMT in patients with breast cancer, an assessment of quality of life can add to the traditional endpoints (toxicity, and disease-free and overall survival) that are routinely assessed in clinical trials. Purpose: This study evaluated the quality of life (QOL) of breast cancer patients who had survived I or more years following high dose chemotherapy with autologous bone marrow transplant (HDC-ABMT) support. Methods: Eighty-two patients who had undergone HDC-ABMT were surveyed by written questionnaire and follow-up telephone interview at least 1 year following HDC-ABMT. Patients were asked to complete the Functional Living Index-Cancer (FLIC), the Symptom Distress Scale (SDS), and a survey of sexual function developed as part of the study. Results: The mean FLIC score among all patients was 130 ± 19.1 (possible range 22–154). FLIC scores were significantly lower in patients with evidence of recurrent disease than in patients who were free of disease. The most commonly reported symptoms after HDC-ABMT were insomnia, fatigue, and pain. Sexual interest and sexual activity were reported to be lower after participation in HDC-ABMT than prior to the procedure. The majority of patients who were employed outside the home prior to HDC-ABMT returned to work with a median time away from work of 48 weeks. Conclusions: Patients with breast cancer who survive 1 or more years following HDC-ABMT rate their QOL at a relatively high level and frequently return to work. Less than one-third of patients who were interviewed reported moderate to severe symptoms. Problems with sexual functioning were common. Implications: Future research is needed on long-term outcomes after HDC-ABMT and on specific areas of concern, such as sexual functioning. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented regarding the use of networking and telephone support groups for male breast cancer patients.

A correction to the article "Long-term psychosocial adjustment of older vs younger survivors of breast and endometrial cancer" that was published in the previous issue is presented.