Search

Caring for older patients with breast cancer presents unique clinical considerations because of preexisting and competing comorbidity, the potential for treatment-related toxicity, and the consequent impact on functional status. In the context of the COVID-19 pandemic, treatment decision making for older patients is especially challenging and encourages us to refocus our treatment priorities. While we work to avoid treatment delays and maintain therapeutic benefit, we also need to minimize the risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposures, myelosuppression, general chemotherapy toxicity, and functional decline. Herein, we propose multidisciplinary care considerations for the aging patient with breast cancer, with the goal to promote a team-based, multidisciplinary treatment approach during the COVID-19 pandemic and beyond. These considerations remain relevant as we navigate the "new normal" for the approximately 30% of breast cancer patients aged 70 years and older who are diagnosed in the United States annually and for the thousands of older patients living with recurrent and/or metastatic disease. [ABSTRACT FROM AUTHOR]

Background: We examined the prognostic significance of circulating tumor cell (CTC) dynamics during treatment in metastatic breast cancer (MBC) patients receiving first-line chemotherapy.Methods: Serial CTC data from 469 patients (2202 samples) were used to build a novel latent mixture model to identify groups with similar CTC trajectory (tCTC) patterns during the course of treatment. Cox regression was used to estimate hazard ratios for progression-free survival (PFS) and overall survival (OS) in groups based on baseline CTCs, combined CTC status at baseline to the end of cycle 1, and tCTC. Akaike information criterion was used to select the model that best predicted PFS and OS.Results: Latent mixture modeling revealed 4 distinct tCTC patterns: undetectable CTCs (56.9% ), low (23.7%), intermediate (14.5%), or high (4.9%). Patients with low, intermediate, and high tCTC patterns had statistically significant inferior PFS and OS compared with those with undetectable CTCs (P < .001). Akaike Information Criterion indicated that the tCTC model best predicted PFS and OS compared with baseline CTCs and combined CTC status at baseline to the end of cycle 1 models. Validation studies in an independent cohort of 1856 MBC patients confirmed these findings. Further validation using only a single pretreatment CTC measurement confirmed prognostic performance of the tCTC model.Conclusions: We identified 4 novel prognostic groups in MBC based on similarities in tCTC patterns during chemotherapy. Prognostic groups included patients with very poor outcome (intermediate + high CTCs, 19.4%) who could benefit from more effective treatment. Our novel prognostic classification approach may be used for fine-tuning of CTC-based risk stratification strategies to guide future prospective clinical trials in MBC. [ABSTRACT FROM AUTHOR]

Background: Hormone receptor signaling is critical in the progression of breast cancers, although the role of the androgen receptor (AR) remains unclear, particularly for estrogen receptor (ER)-negative tumors. This study assessed AR protein expression as a prognostic marker for breast cancer mortality.Methods: This study included 4147 pre- and postmenopausal women with invasive breast cancer from the Nurses' Health Study (diagnosed 1976-2008) and Nurses' Health Study II (1989-2008) cohorts. AR protein expression was evaluated by immunohistochemistry and scored through pathologist review and as a digitally quantified continuous measure. Hazard ratios (HR) and 95% confidence intervals (CI) of breast cancer mortality were estimated from Cox proportional hazards models, adjusting for patient, tumor, and treatment covariates.Results: Over a median 16.5 years of follow-up, there were 806 deaths due to breast cancer. In the 7 years following diagnosis, AR expression was associated with a 27% reduction in breast cancer mortality overall (multivariable HR = 0.73, 95% CI = 0.58 to 0.91) a 47% reduction for ER+ cancers (HR = 0.53, 95% CI = 0.41 to 0.69), and a 62% increase for ER- cancers (HR = 1.62, 95% CI = 1.18 to 2.22) (P heterogeneity < .001). A log-linear association was observed between AR expression and breast cancer mortality among ER- cancers (HR = 1.14, 95% CI = 1.02 to 1.26 per each 10% increase in AR), although no log-linear association was observed among ER+ cancers.Conclusions: AR expression was associated with improved prognosis in ER+ tumors and worse prognosis in ER- tumors in the first 5-10 years postdiagnosis. These findings support the continued evaluation of AR-targeted therapies for AR+/ER- breast cancers. [ABSTRACT FROM AUTHOR]

The article focuses on breast cancer treatment. Topics discussed include use of epidermal growth factor receptor 2 (HER2)–targeted therapies for treating the same; advantages of chemotherapy for treating breast cancer; and risk of developing recurrent breast cancer, and use of complex randomized trial for the same.

The authors discuss the role of intrinsic tumor biology in changing the adjuvant treatment of estrogen receptor-positive disease such as node-positive breast cancer. Topics covered include the function of locoregional recurrence as a surrogate marker of distant disease and survival, the disease-free survival rate in node-positive patients, and the benefits of adjuvant chemotherapy within node-positive luminal tumors.

Background: Tamoxifen use has been associated with increased risk of thromboembolic events (TEs) in women with breast cancer and women at high risk for the disease. Factor V Leiden (FVL) is the most common inherited clotting factor mutation and also confers increased thrombosis risk. We investigated whether FVL was associated with TE risk in women with early-stage breast cancer who took adjuvant tamoxifen. [ABSTRACT FROM PUBLISHER]

A distinctive subset of metastatic breast cancer (MBC) is oligometastatic disease, which is characterized by single or few detectable metastatic lesions. The existing treatment guidelines for patients with localized MBC include surgery, radiotherapy, and regional chemotherapy. The European School of Oncology–Metastatic Breast Cancer Task Force addressed the management of these patients in its first consensus recommendations published in 2007. The Task Force endorsed the possibility of a more aggressive and multidisciplinary approach for patients with oligometastatic disease, stressing also the need for clinical trials in this patient population. At the sixth European Breast Cancer Conference, held in Berlin in March 2008, the second public session on MBC guidelines addressed the controversial issue of whether MBC can be cured. In this commentary, we summarize the discussion and related recommendations regarding the available therapeutic options that are possibly associated with cure in these patients. In particular, data on local (surgery and radiotherapy) and chemotherapy options are discussed. Large retrospective series show an association between surgical removal of the primary tumor or of lung metastases and improved long-term outcome in patients with oligometastatic disease. In the absence of data from prospective randomized studies, removal of the primary tumor or isolated metastatic lesions may be an attractive therapeutic strategy in this subset of patients, offering rapid disease control and potential for survival benefit. Some improvement in outcome may also be achieved with optimization of systemic therapies, possibly in combination with optimal local treatment. [ABSTRACT FROM PUBLISHER]

Compared with treatment options for early-stage breast cancer, few data exist regarding the optimal use of chemotherapy for metastatic breast cancer (MBC). The choice of using a combination of cytotoxic chemotherapies vs sequential single agents is controversial. At the 6th European Breast Cancer Conference, the European School of Oncology Metastatic Breast Cancer Task Force convened an open debate on the relative benefits of combination vs sequential therapy. Based on the available data, the Task Force recommends sequential monotherapy as the preferred choice in advanced disease, in the absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control. Patient- and disease-related factors should be used to choose between combination and sequential single-agent chemotherapy for MBC. Additional research is needed to determine the impact of therapy on patient-rated quality of life and to identify predictive factors that can be used to guide therapy. [ABSTRACT FROM AUTHOR]

Background Adjuvant endocrine treatment with aromatase inhibitors improves disease-free survival compared with tamoxifen in postmenopausal women with estrogen receptor-positive breast cancer. This difference could be due to differences in tamoxifen metabolism because levels of endoxifen, the active tamoxifen metabolite, vary with the number of mutant alleles, including the *4 allele, of the gene encoding cytochrome P450 2D6 (CYP2D6). Methods We created a Markov model to determine whether tamoxifen or aromatase inhibitor monotherapy maximized 5-year disease-free survival for patients with the wild-type CYP2D6 genotype (wt/wt). Annual risks of recurrence with aromatase inhibitors and tamoxifen in breast cancer patients who were not selected by CYP2D6 genotype were derived from the Breast International Group 1-98 trial. Genotype frequencies and the hazard ratio for cancer recurrence on tamoxifen among patients with the *4/*4 genotype relative to the wt/wt or wt/*4 genotypes (HR*4/*4 = 1.86) were based on data from an analysis of the North Central Cancer Treatment Group trial of adjuvant tamoxifen. We explored the impact of CYP2D6(*4) heterozygosity on disease-free survival for wt/wt patients by studying a range of effect (ie, recurrence on tamoxifen) estimates, from no effect of the single mutation (Effwt/*4 = 0, recurrence rate in wt/*4 patients same as that in wt/wt patients) to complete effect (Effwt/*4 = 1, recurrence rate in wt/*4 patients same as that in *4/*4 patients). Results With HR*4/*4 = 1.86 and Effwt/*4 = 0.5, the 5-year disease-free survival of tamoxifen-treated patients with no mutations (wt/wt) was 83.9%, that is, essentially the same as that (84.0%) for genotypically unselected patients who were treated with aromatase inhibitors. With greater HR*4/*4 estimates, disease-free survival with tamoxifen exceed that with aromatase inhibitors in wt/wt patients, even at lower assumed Effwt/*4 ratios. Conclusions Modeling suggests that among patients who are wild type for CYP2D6, 5-year disease-free survival outcomes are similar to or perhaps even superior with tamoxifen than with aromatase inhibitors. Endocrine therapy tailored to CYP2D6 genotype could be considered for women who are newly diagnosed with breast cancer, particularly those who have with concerns about either the relative toxicity or the increased cost of aromatase inhibitors. [ABSTRACT FROM AUTHOR]

Background Ductal carcinoma in situ (DCIS) has a generally favorable overall prognosis, with a systemic recurrence rate of approximately 1%, a local recurrence rate after mastectomy of 1%, and a local recurrence rate after breast-conserving treatment of less than 10%. Preliminary studies have suggested that women with DCIS may overestimate their risk of disease recurrence. Few data exist regarding psychosocial outcomes for women with DCIS. Methods Women in Eastern Massachusetts with newly diagnosed DCIS were asked to participate in a longitudinal study of risk perceptions, psychosocial concerns, and health behaviors. Psychosocial outcomes after DCIS diagnosis and risk perceptions were evaluated at enrollment and at 9 and 18 months. All statistical tests were two-sided. Results Four hundred eighty-seven women with DCIS (64% of eligible participants) completed the enrollment survey. Overall quality of life was good among the women surveyed, and the substantial anxiety at enrollment decreased with time (P < .001). At enrollment, 54% perceived at least a moderate risk for DCIS recurrence in the next 5 years, 68% in their lifetime; 39% perceived at least a moderate risk for invasive cancer in the next 5 years, 53% in their lifetime; and 28% perceived at least a moderate likelihood of DCIS spreading to other places in their body. At 18 months after enrollment, perceived risks had not statistically significantly changed from those at enrollment (P = .38). Anxiety at enrollment was the factor that was most consistently and strongly associated with overestimation of future breast cancer-related risks (perceived moderate or greater risk vs less than moderate risk of DCIS recurring within 5 years: odds ratio [OR] = 4.0, 95% confidence interval [CI] = 1.6 to 9.9, P= .003; of invasive breast cancer within 5 years: OR = 4.3, 95% CI = 1.9 to 9.9, P < .001; and of invasive breast cancer during lifetime: OR = 5.3, 95% CI = 2.0 to 14.3, P < .001). Conclusions Many women with newly diagnosed DCIS have inaccurate perceptions of the breast cancer risks that they face, and anxiety is particularly associated with these inaccurate perceptions. [ABSTRACT FROM AUTHOR]

Despite recent interest on the part of advocates and researchers of oncology clinical trials in sharing study results, participants in these trials are not routinely informed about the results. We identified oncology physicians and nurses through the Cancer and Leukemia Group B database and surveyed them about sharing clinical trial results with participants. Of 1977 eligible members, 796 (40.3%) responded to the mailed survey, 497 (62.4%) of whom reported that they offer trial results to participants less than one-fifth of the time. A total of 576 (72.4%) of responders believed that most patients want to know the results of studies, and 634 (79.7%) of responders expressed willingness to offer results to most study participants in the future, believing that most patients want to know trial results and that routinely offering results would not have a negative effect on patients. Concerns of some responders about routinely offering trial results included negative emotional effect on patients, patient difficulty understanding the information, and resources required to offer the results. Of concern, 16.2% (129⁄796) of responders believed an obligation to offer results to study participants would make them less likely to enroll patients on studies. Future studies should consider sharing trial results with patients and evaluating the process and its effect on both patients and clinicians. [ABSTRACT FROM AUTHOR]

With the rise in availability and increasing use of oral anticancer agents, concerns about adherence to prescribed regimens will become an increasingly important issue in oncology. Few published studies have focused on adherence to oral antineoplastic therapy, in part because the vast majority of chemotherapy is delivered intravenously in physicians' offices or hospitals. In this article, we review current knowledge of adherence behavior with regard to oral medications in general, including factors associated with adherence and methods for measuring adherence. We also review published studies of adherence to oral antineoplastic agents in adult and pediatric populations and adherence issues in cancer prevention. The available evidence reveals that patient adherence to oral chemotherapy recommendations is variable and not easily predicted. Adherence rates ranging from less than 20% to 100% have been reported, and certain populations, such as adolescents, pose particular challenges. Future efforts should focus on improving measurement and prediction of adherence and on developing interventions to improve adherence for both patients in clinical trials and patients being treated outside of the research setting. Assessment of adherence among individuals with cancer and implementation of interventions in situations of poor adherence should improve clinical outcomes. [ABSTRACT FROM AUTHOR]

The decision to receive chemotherapy or chemohormonal therapy involves careful consideration of both the potential benefits and possible risks of therapy. There are substantial short- and long-term side effects from chemotherapy. By convention, short-term side effects include those toxic effects encountered during chemotherapy, while long-term side effects include later complications of treatment arising after the conclusion of adjuvant chemotherapy. These side effects vary, depending on the specific agents used in the adjuvant regimen as well as on the dose used and the duration of treatment. There is also considerable variability in side effect profile across individuals. This review will focus on the short- and long-term toxicity seen with the most commonly used adjuvant chemotherapy and chemohormonal therapy regimens. [ABSTRACT FROM AUTHOR]

: P-glycoprotein mediates resistance to natural-product anti-neoplastic agents like vinblastine through an active transport process resulting in reduced intracellular concentration of these agents. The triphenylethylene antiestrogen tamoxifen and its major metabolite -desmethyltamoxifen at concentrations of 4–6 μ enhance the intracellular concentration of natural-product antineoplastics and augment the cytotoxicity of such drugs three-fold to 10-fold in a variety of human and murine cell lines. : On the basis of these preclinical findings, we conducted a phase I clinical trial of high-dose, oral tamoxifen administered in conjunction with a 5-day continuous infusion of vinblastine. : We studied 53 patients with advanced epithelial tumors. Tamoxifen was given orally as a loading dose on day 1, followed by two doses a day on days 2–13. Vinblastine was given as a 120-hour continuous infusion (1.5 mg/m per day) on days 9–13 of each tamoxifen course. The starting dose of tamoxifen was 40 mg/m administered twice a day following a loading dose of 150 mg/m. The maximum dose was 260 mg/m twice a day following a loading dose of 680 mg/m. Treatment cycles were repeated every 28 days. : The dose-limiting toxic effects of tamoxifen were neurologic and began within 3–5 days after the start of treatment. They consisted of tremor, hyperreflexia, dysmetria, unsteady gait, and dizziness. One patient experienced a grand mal seizure 24 hours after the last tamoxifen dose. Toxic effects were rapidly reversible. Asymptomatic prolongation of the QT interval on electrocardiogram occurred at doses of tamoxifen of 80 mg/m or higher given twice a day. No coagulation or ophthalmologic abnormalities occurred. Tamoxifen did not enhance the toxicity of vinblastine. Mean plasma concentrations of tamoxifen or -desmethyltamoxifen at 260 mg/m tamoxifen given twice a day for 13 days were 6.04 and 6.56 μ, respectively. There was no relationship between plasma antiestrogen content and the development of neurotoxic effects. : Tamoxifen at 150 mg/m given twice a day following a loading dose of 400 mg/m results in plasma levels of tamoxifen and -desmethyltamoxifen of 4 and 6 μ, respectively, without dose-limiting toxicity. We recommend this dose for phase II trials of tamoxifen to modulate P-glycoprotein-mediated drug resistance. : Our study demonstrates that high-dose tamoxifen can be safely administered and that plasma concentrations that may inhibit P-glycoprotein function can be achieved. [J Natl Cancer Inst 84:1811–1816, 1992] [ABSTRACT FROM PUBLISHER]

A response by Jennifer A. Ligibel and colleagues to a letter to the editor about their article "Body Mass Index, PAM50 Subtype, and Outcomes in Node-Positive Breast Cancer: CALGB 9741," published in a previous issue is presented.

A response by Fatima Cardoso and colleagues to a letter to the editor about their article "International Guidelines for Management of Metastatic Breast Cancer: Combination vs. Sequential Single-Agent Chemotherapy" in a 2009 issue of the journal is presented.

A response by Rinaa S. Punglia and colleagues to a letter to the editor on the article "Pharmacogenomic variation of CYP2D6 and the choice of optimal adjuvant endocrine therapy for postmenopausal breast cancer: a modeling analysis," that was published in the previous issue is presented.

Presents a letter to the editor of the 'Journal of the National Cancer Institute,' which asserts that results of clinical trials of cancer treatments, whether positive or negative, should be made available to participants and that providing results should be considered the ethical norm. Participants' preference for getting the results from doctors, instead of other members of the research team.