Five-year invasive disease–free survival was similar among postmenopausal women with hormone-receptor–positive, HER2-negative breast cancer, one to three positive axillary lymph nodes, and a 21-gene ...recurrence score of 25 or lower who received endocrine-only therapy and those who received chemoendocrine therapy. In premenopausal women, chemoendocrine therapy significantly improved outcomes.
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.
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.
Abstract Rationale Breast cancer is a disease of ageing. Functional independence in elderly patients, measured with the Katz activities of daily living (ADL) scale, predicts overall survival and the ...need for welfare support. Few prospective studies have examined the feasibility of adjuvant chemotherapy and its impact on autonomy in women over 70 years of age with high-risk breast cancer. This multicentre phase II trial was designed to assess the impact of adjuvant anthracycline-based chemotherapy on these patients’ autonomy. Design and methods In a two-stage Fleming design, women aged ≥70 years with histologically proven hormone-receptor-negative early breast cancer and a significant risk of recurrence (pN+ or “high risk” pN0) received 4 cycles of nonpegylated liposomal doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks postoperatively, on an outpatient basis. The primary endpoint was the change in the ADL score during chemotherapy. Secondary endpoints include comprehensive geriatric, quality-of-life and acceptability assessments, tolerability, and long-term outcome. The results for the primary endpoint and other scales at completion of adjuvant chemotherapy are reported here, while long-term follow-up is not yet complete. Results Forty patients (median age 75 70–82) were enrolled between February 2006 and November 2007. Chemotherapy had no deleterious impact on ADL, cognition, mental status, or the frequency of comorbidities. In contrast, the number of patients at risk of malnutrition, based on the Mini Nutritional Assessment, more than doubled between baseline and the end of chemotherapy, rising from 15% to 38%. Quality-of-life deteriorated in terms of social and role functioning, likely owing to fatigue, loss of appetite, nausea and vomiting. Treatment acceptability was good. The main adverse effect was neutropenia, 15% of the patients experiencing febrile neutropenia. No cardiac toxicity or toxic deaths occurred. Conclusion This study demonstrates the feasibility of an adjuvant chemotherapy regimen combining nonpegylated liposomal doxorubicin and cyclophosphamide in fit elderly women <85 years with breast cancer. Although chemotherapy had an impact on social and role functioning, autonomy was not impaired and toxicity was acceptable. Special attention should be paid to nutritional status before and after treatment.
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.
CONTEXT Adjuvant chemotherapy with new cytotoxic agents for breast cancer must
be properly assessed for toxicity. OBJECTIVE To describe adverse events associated with adjuvant chemotherapy for
breast ...cancer, which led to premature termination of a clinical trial. DESIGN, SETTING, AND PATIENTS We conducted a prospective randomized multicenter study (Reposant sur
des Arguments Pronostiques et Prédictifs RAPP-01) to compare the
effectiveness of 2 chemotherapy regimens. Patients (women aged 18-70 years)
had primary unilateral breast cancer and either a moderate number of positive
axillary lymph nodes (≤3) or no positive axillary lymph nodes (N0), but
were at a high risk of relapse. Patients were treated at 11 French cancer
referral centers from June 1999 through January 2003. Primary prophylaxis
for febrile neutropenia was not recommended in the study protocol. INTERVENTIONS Doxorubicin, 50 mg/m2, plus docetaxel, 75 mg/m2,
or doxorubicin, 60 mg/m2, plus cyclophosphamide, 600 mg/m2, given postoperatively for 4 courses. MAIN OUTCOME MEASURES The main end point was the disease-free survival rate at 5 years, as
estimated using the Kaplan-Meier product limit method. Secondary end points
included safety, which is the focus of this article, and overall survival. RESULTS A total of 627 women were enrolled. Median follow-up is currently too
short (24 months) to analyze the primary end point. The trial was terminated
prematurely when 2 deaths related to drug toxicity and 1 case of perforative
peritonitis occurred among patients with febrile neutropenia, all in the doxorubicin-docetaxel
group. The incidence of febrile neutropenia was significantly higher with
the doxorubicin-docetaxel regimen (40.8%) than with the doxorubicin-cyclophosphamide
regimen (7.1%) (P<.001). CONCLUSIONS A high risk of life-threatening complications associated with the doxorubicin-docetaxel
regimen was found in this open-label controlled trial. The doxorubicin-docetaxel
combination should not be considered as an alternative to the doxorubicin-cyclophosphamide
regimen outside carefully designed studies that include primary prophylaxis
for febrile neutropenia.