The recurrence score based on the 21-gene breast-cancer assay has been clinically useful in predicting a chemotherapy benefit in hormone-receptor-positive, human epidermal growth factor receptor 2 ...(HER2)-negative, axillary lymph-node-negative breast cancer. In women with positive lymph-node disease, the role of the recurrence score with respect to predicting a benefit of adjuvant chemotherapy is unclear.
In a prospective trial, we randomly assigned women with hormone-receptor-positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a recurrence score of 25 or lower (scores range from 0 to 100, with higher scores indicating a worse prognosis) to endocrine therapy only or to chemotherapy plus endocrine (chemoendocrine) therapy. The primary objective was to determine the effect of chemotherapy on invasive disease-free survival and whether the effect was influenced by the recurrence score. Secondary end points included distant relapse-free survival.
A total of 5083 women (33.2% premenopausal and 66.8% postmenopausal) underwent randomization, and 5018 participated in the trial. At the prespecified third interim analysis, the chemotherapy benefit with respect to increasing invasive disease-free survival differed according to menopausal status (P = 0.008 for the comparison of chemotherapy benefit in premenopausal and postmenopausal participants), and separate prespecified analyses were conducted. Among postmenopausal women, invasive disease-free survival at 5 years was 91.9% in the endocrine-only group and 91.3% in the chemoendocrine group, with no chemotherapy benefit (hazard ratio for invasive disease recurrence, new primary cancer breast cancer or another type, or death, 1.02; 95% confidence interval CI, 0.82 to 1.26; P = 0.89). Among premenopausal women, invasive disease-free survival at 5 years was 89.0% with endocrine-only therapy and 93.9% with chemoendocrine therapy (hazard ratio, 0.60; 95% CI, 0.43 to 0.83; P = 0.002), with a similar increase in distant relapse-free survival (hazard ratio, 0.58; 95% CI, 0.39 to 0.87; P = 0.009). The relative chemotherapy benefit did not increase as the recurrence score increased.
Among premenopausal women with one to three positive lymph nodes and a recurrence score of 25 or lower, those who received chemoendocrine therapy had longer invasive disease-free survival and distant relapse-free survival than those who received endocrine-only therapy, whereas postmenopausal women with similar characteristics did not benefit from adjuvant chemotherapy. (Funded by the National Cancer Institute and others; RxPONDER ClinicalTrials.gov number, NCT01272037.).
The objective of this phase II trial was to assess the efficacy and toxicity of weekly paclitaxel for patients with metastatic or unresectable angiosarcoma.
Thirty patients were entered onto the ...study from April 2005 through October 2006. Paclitaxel was administered intravenously as a 60-minute infusion at a dose of 80 mg/m(2) on days 1, 8, and 15 of a 4-week cycle. The primary end point was the nonprogression rate after two cycles.
The progression-free survival rates after 2 and 4 months were 74% and 45%, respectively. With a median follow-up of 8 months, the median time to progression was 4 months and the median overall survival was 8 months. The progression-free survival rate was similar in patients pretreated with chemotherapy and in chemotherapy-naïve patients (77% v 71%). Three patients with locally advanced breast angiosarcoma presented partial response, which enabled a secondary curative-intent surgery with complete histologic response in two cases. One toxic death occurred as a result of a thrombocytopenia episode. Six patients presented with grade 3 toxicities and one patient presented with a grade 4 toxicity. Anemia and fatigue were the most frequently reported toxicities.
Weekly paclitaxel at the dose schedule used in the current study was well tolerated and demonstrated clinical benefit.
Breast cancer is increasingly prevalent in older adults and is a substantial part of routine oncology practice. However, management of breast cancer in this population is challenging because the ...disease is highly heterogeneous and there is insufficient evidence specific to older adults. Decision making should not be driven by age alone but should involve geriatric assessments plus careful consideration of life expectancy, competing risks of mortality, and patient preferences. A multidisciplinary taskforce, including members of the European Society of Breast Cancer Specialists and International Society of Geriatric Oncology, gathered to expand and update the previous 2012 evidence-based recommendations for the management of breast cancer in older individuals with the endorsement of the European Cancer Organisation. These guidelines were expanded to include chemotherapy toxicity prediction calculators, cultural and social considerations, surveillance imaging, genetic screening, gene expression profiles, neoadjuvant systemic treatment options, bone-modifying drugs, targeted therapies, and supportive care. Recommendations on geriatric assessment, ductal carcinoma in situ, screening, primary endocrine therapy, surgery, radiotherapy, adjuvant systemic therapy, and secondary breast cancer were updated.
Adjuvant systemic treatments for older patients with breast cancer require constant dose or schedule adjustments of standards established for younger ones. This is mainly due to frailty that ...increases according to age (40%-50% of signals in all comers after age 70 years) and remains difficult to spot or diagnose accurately and therefore is often overlooked. Older patients are at higher risk to develop side effects whether under chemotherapy, optimized endocrine treatment, or targeted therapies. Pharmacokinetic reflects poorly functional reserves that reduce with aging and is therefore misleading. The demonstration of significant long-term benefits provided by adjuvant treatments is challenged by life expectancy, driven by multimorbidity status that increases with age, competing with cancer outcome. When geriatric assessment is incorporated into the multidisciplinary team, treatment decision process shows 30%-50% changes, de-escalating initial age-agnostic treatment choices in two of three cases. Finally, expectations from treatment vary over the years: In older ones, although not being exclusive, there is a general shift of preference for protecting functionality, cognitive functions, and independence, as summarized in quality of life that many systemic adjuvant treatment may jeopardize. These provocative considerations show importance to pay more attention to expectations expressed by older patients to limit gaps between what is thought by health care professionals as right, often on the basis of dose intensity models strongly engrained in oncology and that older patients may assess counterintuitively differently. The most achieved molecular testing to identify high-risk luminal tumors should be combined with determinant geriatric factors to bring relevant global information in the adjuvant setting for older patients.
There is currently no guidance on how to approach surveillance mammography for older breast cancer survivors, particularly when life expectancy is limited.
To develop expert consensus guidelines that ...facilitate tailored decision-making for routine surveillance mammography for breast cancer survivors 75 years or older.
After a literature review of the risk of ipsilateral and contralateral breast cancer events among breast cancer survivors and the harms and benefits associated with mammography, a multidisciplinary expert panel was convened to develop consensus guidelines on surveillance mammography for breast cancer survivors 75 years or older. Using an iterative consensus-based approach, input from clinician focus groups, and critical review by the International Society for Geriatric Oncology, the guidelines were refined and finalized.
The literature review established a low risk for ipsilateral and contralateral breast cancer events in most older breast cancer survivors and summarized the benefits and harms associated with mammography. Draft mammography guidelines were iteratively evaluated by the expert panel and clinician focus groups, emphasizing a patient's risk for in-breast cancer events, age, life expectancy, and personal preferences. The final consensus guidelines recommend discontinuation of routine mammography for all breast cancer survivors when life expectancy is less than 5 years, including those with a history of high-risk cancers; consideration to discontinue mammography when life expectancy is 5 to 10 years; and continuation of mammography when life expectancy is more than 10 years. Individualized, shared decision-making is encouraged to optimally tailor recommendations after weighing the benefits and harms associated with surveillance mammography and patient preferences. The panel also recommends ongoing clinical breast examinations and diagnostic mammography to evaluate clinical findings and symptoms, with reassurance for patients that these practices will continue.
It is anticipated that these expert guidelines will enhance clinical practice by providing a framework for individualized discussions, facilitating shared decision-making regarding surveillance mammography for breast cancer survivors 75 years or older.
Summary As the mean age of the global population increases, breast cancer in older individuals will be increasingly encountered in clinical practice. Management decisions should not be based on age ...alone. Establishing recommendations for management of older individuals with breast cancer is challenging because of very limited level 1 evidence in this heterogeneous population. In 2007, the International Society of Geriatric Oncology (SIOG) created a task force to provide evidence-based recommendations for the management of breast cancer in elderly individuals. In 2010, a multidisciplinary SIOG and European Society of Breast Cancer Specialists (EUSOMA) task force gathered to expand and update the 2007 recommendations. The recommendations were expanded to include geriatric assessment, competing causes of mortality, ductal carcinoma in situ, drug safety and compliance, patient preferences, barriers to treatment, and male breast cancer. Recommendations were updated for screening, primary endocrine therapy, surgery, radiotherapy, neoadjuvant and adjuvant systemic therapy, and metastatic breast cancer.
CirCe01 trial aimed to assess the clinical utility of circulating tumour cell (CTC)-based monitoring in metastatic breast cancer (MBC) patients beyond the third line of chemotherapy (LC).
CirCe01 was ...a prospective, multicentre, randomised trial (NCT01349842) that included patients with MBC after two systemic LC. Patients with ≥5 CTC/7.5 mL (CellSearch®) were randomised between the CTC-driven and the standard arm. In the CTC arm, changes in CTC count were assessed at the first cycle of each LC; patients in whom CTC levels predicted early tumour progression had to switch to a subsequent LC.
Greater than or equal to 5 CTC/7.5 mL were observed in N = 101/204 patients. In the CTC arm (N = 51), 43 (83%) and 18 (44%) patients completed CTC monitoring in the third and fourth lines, respectively, and 18 (42%) and 11 (61%) of these patients, respectively, had no CTC response. Thirteen (72%) and 5 (46%) of these patients underwent early switch to the next LC. Overall survival was not different between the two arms (hazard ratio = 0.95, 95% confidence interval = 0.6;1.4, p = 0.8). In subgroup analyses, patients with no CTC response who switched chemotherapy experienced longer survival than patients who did not.
Due to the limited accrual and compliance, this trial failed to demonstrate the clinical utility of CTC monitoring.
NCT, NCT01349842, https://clinicaltrials.gov/ct2/show/NCT01349842 , registered 9 May 2011.
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