Chemotherapy In Older Women Research Articles

Adjuvant Chemotherapy in Older Women with Early-Stage Breast Cancer

Adjuvant Chemotherapy in Older Women with Early-Stage Breast Cancer

Adjuvant Chemotherapy in Older Women with Early-Stage Breast Cancer

Adjuvant Chemotherapy in Older Women with Early-Stage Breast Cancer

Risk of subsequent dementia diagnoses does not vary by types of adjuvant chemotherapy in older women with breast cancer

Little is known about long-term cognitive side effects of adjuvant chemotherapy for breast cancer. We thus examined incidence of dementia diagnoses in older women diagnosed with breast cancer, stratified by types of chemotherapy regimen. We identified patients with incident dementia diagnoses through Medicare claims linked to the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) tumor registry data. The study population (n = 6,932) consisted of women at least 68 years of age, who were diagnosed with early-stage breast cancer from 1994 through 2002 in one of the SEER areas and received chemotherapy as part of their cancer treatment. Excluded were women with a diagnosis of dementia within the 3 years prior to their cancer diagnosis. Our sample comprised mostly white women. The mean age was 74. Fifty-seven percent were estrogen receptor positive. Over 70% had no comorbidity. The use of taxol and anthracycline-based treatments increased from mid-1990s to early 2000. Increasing age at cancer diagnosis, Black ethnicity, living in a census tract with lower level of education, and increasing number of comorbidities were associated with new claims of dementia diagnoses after chemotherapy. There was no significant association between types of chemotherapy agents and risk of subsequent dementia diagnoses. No association was found between types of adjuvant chemotherapy agents for breast cancer and risk of new dementia diagnoses. Our findings suggest that concerns about post-chemotherapy dementia should not be a major factor in determining type of adjuvant chemotherapy regimen to prescribe for older women with breast cancer.

New Treatment Strategies Provide More Options for Patients With Breast Cancer

CHICAGO—Recently completed clinical trials indicate that new treatment strategies may control disease and improve survival for patients with breast cancer, in some cases in advanced disease. The findings, presented here at the annual meeting of the American Society of Clinical Oncology in June, suggest that patients with breast cancer will soon have more options for treating the disease. “We have a multitude of therapies for women with breast cancer but continue to need new treatments that are more effective and have fewer side effects,” said Eric Winer, MD, professor of medicine at Harvard Medical School and director of the Breast Oncology Center at the Dana-Farber Cancer Institute, both in Boston. In 2008, about 182 460 new cases of invasive breast cancer will be diagnosed among women in the United States, according to estimates by the American Cancer Society. An additional 67 770 US women will be diagnosed in 2008 with the earliest, noninvasive form of breast cancer, carcinoma in situ. “Among women who have early stage breast cancer, our goal is to prevent recurrences and ultimately to prevent death from breast cancer while minimizing the side effects from treatment,” Winer said. “And in women with late-stage or metastatic breast cancer . . . our goal is to maintain quality of life, to control the disease, and to extend the period of time that a woman is alive with cancer.” Studies presented at the conference indicate that zoledronic acid can help prevent recurrence in early stage breast cancer, that adding bevacizumab to docetaxel slows disease progression in patients newly diagnosed as having locally advanced or metastatic breast cancer, and that the oral chemotherapy agent capecitabine is not an acceptable replacement for standard adjuvant chemotherapy in older women.

Feasibility and toxicity of dose-dense adjuvant chemotherapy in older women with breast cancer

The objective of this study was to examine the feasibility and toxicity of adjuvant dose-dense chemotherapy in older women with breast cancer. A search of the Memorial Sloan-Kettering Cancer Center (MSKCC) breast cancer database was performed to identify all patients age 60 and older who underwent an initial consultation with a breast medical oncologist between October 1, 2002 and June 28, 2005. Inclusion criteria were: (1) age > or = 60, (2) follow-up care obtained at MSKCC, (3) intent to treat with adjuvant dose-dense AC-T (doxorubicin 60 mg/m(2) and cyclophosphamide 600 mg/m(2) every 2 weeks for 4 cycles followed by paclitaxel 175 mg/m(2) every 2 weeks for 4 cycles, with white blood cell growth factor support). One hundred sixty-two patients (mean age 66, range 60-76) with breast cancer, stages I (n = 5), II (n = 111), and III (n = 46) according to the sixth edition of the AJCC staging system, were included in this analysis. Forty-one percent (n = 67) experienced a grade 3 or 4 toxicity, 9% a grade 3 infection (n = 14), 6% grade 3 fatigue (n = 9), 5% neutropenic fever (n = 8), and 4% thromboembolic events (n = 7). Twenty-two percent (n = 36) did not complete the planned 8 cycles of treatment. There was no statistically significant association between age and either toxicity or treatment discontinuation. In multivariate analysis including age, pretreatment hemoglobin, and comorbidity, the presence of comorbidity (Charlson score > or = 1) and a lower baseline hemoglobin score were associated with an increased risk of any grade 3 or 4 toxicity. We found that the risk of toxicity depended more on comorbid medical conditions and baseline hemoglobin value than age in this cohort of older adults receiving dose-dense adjuvant chemotherapy.

Gene expression determinants of ovarian cancer platinum-response in older women

22059 Background: Epithelial ovarian cancer (EOC) is the most lethal gynecologic malignancy, and more than half of new ovarian cancer cases arise in women over age 65. Although older women with EOC have poorer overall prognosis compared to younger women, the exact molecular basis to this difference remains unclear. The goal of this study is to improve our understanding of the molecular underpinnings of advanced stage EOC in older women and identify genes associated with chemo-response in older women such that therapy may be tailored to individual patients. Methods: We performed Affymetrix microarray gene expression analysis on 122 primary advanced stage epithelial ovarian cancers resected from 73 younger (<65 years) and 49 older (>65 years) women. For each age group, gene expression data was compared using Significance Analysis of Microarrays (SAM), between patients who demonstrated a complete-response (>65 years, n=38; <65 years, n=48) and incomplete-response (>65 years, n=11; <65 years, n=25) to primary platinum-based chemotherapy. Differential expression was determined by two class unpaired t-tests (false discovery rate, 0%), and results ranked according to d score. Results: We identified 317 genes associated with platinum-response in cancers from younger women, and 264 genes associated with platinum-response in cancers from older women. Six genes (JRKL, LRP8, OVOL2, PKP4, SRD5A1, TMEM1) demonstrated differential expression associated with platinum-response in cancers from both age groups. Genes associated with platinum-response in older, but not younger, women have functional links to apoptosis regulation, programmed cell death, and cell growth. In contrast, genes associated with platinum-response in younger women have functional links to DNA repair. Conclusions: We have identified genes associated with response to platinum-based therapy in younger and older women with EOC. Our data provides insights into biologic functions that may underlie differences in chemo-responsiveness in older versus younger women with EOC. Identifying the molecular underpinnings that drive response to chemotherapy in older women may enable clinicians to tailor therapy and identify potential novel therapeutic targets. No significant financial relationships to disclose.

Editorial: Gene Expression Profile Assays As an Aid in Treatment Decision Making in Early-Stage Breast Cancer

Each year, more than 200,000 women in the United States are diagnosed with invasive breast cancer, and approximately 40,000 die from the disease.1 Nearly half of these women present with hormone receptor–positive, lymph node– negative disease, a subgroup that has increased in size due largely to routine breast cancer screening and increased awareness. Currently, the decision to treat early-stage breast cancer with adjuvant chemotherapy and hormonal therapy is based on clinical and histologic criteria including tumor size, grade, hormone receptor status, human epidermal growth factor receptor (HER-2)/neu overexpression, and the presence or absence of lymph node involvement. Patient menopausal status may affect treatment decisions due to presumed lower recurrence risk and both smaller benefit and greater toxicity with systemic chemotherapy in older women. Clinical practice guidelines recommend adjuvant chemotherapy as well as hormonal therapy for most women with hormone receptor–positive, lymph node– negative early-stage breast cancer. However, the majority of women with hormone receptor–positive lymph node–negative, breast cancer do not develop distant recurrence or death even in the absence of adjuvant chemotherapy. In addition, systemic chemotherapy is associated with both immediate and delayed toxicity, as well as considerable cost.2,3 At the same time, randomized controlled trials have shown that adjuvant chemotherapy is beneficial in some women with early-stage breast cancer, while others will develop distant metastases despite receiving chemotherapy.4 Many breast cancer patients therefore continue to be either overtreated or undertreated with adjuvant chemotherapy due to the lack of sufficiently accurate prognostic and predictive information. The availability of high-performance screening techniques using DNA microarrays has permitted analysis of gene expression patterns and study of their relationship to the risk of disease recurrence as well as treatment effectiveness, in an effort to guide clinicians in their daily decisions on the use of systemic adjuvant therapy.

The Institute of Cancer Research, Clinical Trials and Statistics Unit (ICR-CTSU)

This section provides current contact details and a summary of recent or ongoing clinical trials being coordinated by The Institute of Cancer Research, Clinical Trials and Statistics Unit (ICR-CTSU). Clinical trials include: The NCRI Adjuvant Breast Cancer (ABC) trial. ISRCTN31514446The UK randomized trial of hormone replacement therapy (HRT) in women with a history of early stage breast cancer. ISRCTN29941643NCRI Standardisation of Breast Radiotherapy (START) trial. ISRCTN59368779TACT: A randomized trial of standard anthracycline-based chemotherapy (fluorouracil, epirubicin and cyclophosphamide (FEC) or epirubicin and CMF (Epi-CMF)) versus FEC followed by sequential docetaxel in women with early breast cancer. ISRCTN 79718493SoFEA: Study of Faslodex with or without concomitant Arimidex versus Exemestane following progression on non-steroidal Aromatase inhibitors. ISRCTN: 44195747TACT2: Trial of accelerated adjuvant chemotherapy with Capecitabine in early breast cancer. ISRCTN68068041FAST trial: Prospective randomized clinical trial testing 5.7 Gy and 6.0 Gy fractions of whole breast radiotherapy in terms of late normal tissue responses and tumour control.IMPORT low trial.IMPORT high trial.Adjuvant chemotherapy in older women (ACTION).

Adjuvant Chemotherapy and Survival in Older Women With Hormone Receptor–Negative Breast Cancer: Assessing Outcome in a Population-Based, Observational Cohort

For older breast cancer patients, there is limited evidence of the efficacy of adjuvant chemotherapy from randomized clinical trials. Our goal was to assess the relationship between adjuvant chemotherapy use and survival in a large, population-based cohort of older women with hormone receptor (HR) -negative breast cancer. We identified women age 66 and older diagnosed with HR-negative, nonmetastatic breast cancer from 1992 to 1999 in the Surveillance, Epidemiology and End Results (SEER) cancer registries. Chemotherapy use was identified in Medicare claims linked to SEER records. Clinical and sociodemographic predictors of chemotherapy use were identified using logistic regression. The effect of chemotherapy on survival was evaluated using propensity score methods and multivariable proportional hazards regression. A total of 1,711 (34%) of 5,081 women with HR-negative breast cancer received chemotherapy within 6 months of cancer diagnosis. Chemotherapy use decreased with increasing age and comorbidity, and increased with year of diagnosis, tumor size, number of positive lymph nodes, and higher tumor grade. Adjuvant chemotherapy was associated with a mortality reduction of approximately 15% whether analyzed using propensity scores or standard multivariable methods. The greatest overall survival benefit was observed in patients with node-positive disease and in the node-negative patients most likely to receive chemotherapy. This analysis suggests a survival benefit from adjuvant chemotherapy in older women with HR-negative breast cancer. The benefit of chemotherapy is most pronounced in the patients most likely to be selected for treatment, including those with involved lymph nodes or other high-risk disease characteristics.

Use and Outcomes of Adjuvant Chemotherapy in Older Women With Breast Cancer

This study was undertaken to determine patterns and outcomes of adjuvant chemotherapy use in a population-based cohort of older women with primary breast cancer. Women were identified from the Surveillance, Epidemiology, and End Results-Medicare-linked database who met the following criteria: age > or = 65 years, stage I to III breast cancer, and diagnosis between 1991 and 1999. Adjuvant chemotherapy use was ascertained by Common Procedural Terminology J codes. Logistic regression analysis was performed to determine factors associated with chemotherapy use. Multivariate Cox proportional hazards models were used to calculate the hazard of death for women with and without chemotherapy. A total of 41,390 women met study criteria, of whom 4,500 (10.9%) received chemotherapy. The use of adjuvant chemotherapy more than doubled during the 1990s, from 7.4% in 1991 to 16.3% in 1999 (P < .0001), with a significant shift toward anthracycline use. Women who were younger, white, with lower comorbidity scores, more advanced stage disease, and estrogen receptor (ER) -negative disease were significantly more likely to receive chemotherapy. Chemotherapy was not associated with improved survival among women with lymph node-negative (LN) disease or LN-positive, ER-positive disease (hazard ratio [HR], 1.05; 95% CI, 0.85 to 1.31). However, among women with LN-positive, ER-negative breast cancer, chemotherapy was associated with a significant reduction in breast cancer mortality (HR, 0.72; 95% CI, 0.54 to 0.96). A similar significant benefit of chemotherapy was seen in the subset of women age 70 years or older (HR, 0.74; 95% CI, 0.56 to 0.97). In this observational cohort, chemotherapy was associated with a significant reduction in mortality among older women with ER-negative, LN-positive breast cancer.

Psychosocial Determinants and Outcomes of Chemotherapy in Older Women with Breast Cancer

With the aging of the U.S. population and rising breast cancer incidence with advancing age, the absolute number of women aged 65 years and older diagnosed with and surviving breast cancer will dramatically increase over the coming decades. Despite this demographic imperative, we know little about the impact of adjuvant therapies in this age group. We synthesized data to describe key findings and gaps in knowledge about the outcomes of adjuvant breast cancer treatment in women aged 65 years and and older ("older women"). We reviewed research published between 1995 and June 2005 on breast cancer outcomes among older women treated with adjuvant therapy for breast cancer. Outcomes included communication, emotional distress, satisfaction, and multiple quality-of-life domains. Only 16 articles focused exclusively on older women and chemotherapy; and only one included a large sample of older women (N = 1755). Most common domains included comorbidities, symptoms, and survival. Of the 13 clinical trials and three observational studies we reviewed, only one clinical trial measured quality of life and psychological factors such as coping. None of the studies examined patient preferences or patient-physician communication (processes of care) in older women. Few studies have been designed to specifically evaluate adjuvant therapy processes and outcomes among older women, especially interactions between treatment and comorbidity, and the impact of the processes of care on outcomes. In addition, only narrow segments of the older population with breast cancer (e.g., well-educated, nonminority women) have been included in trials to date. Thus, at present we do not have sufficient data to assist physicians and their older patients in developing adjuvant treatment decisions and plans tailored to older women's needs, preferences, and concerns.

Squaring the Circle: Adjuvant Chemotherapy for Older Women With Breast Cancer

Squaring the Circle: Adjuvant Chemotherapy for Older Women With Breast Cancer

Chemotherapy for older women with early breast cancer

The incidence of breast cancer increases with age, reaching over 300 per 100,000 in women aged 70-75 years in the U.K., increasing to almost 400 per 100,000 in women aged over 85 years. As a healthy 70-year old woman can now expect to live for an average of 15 years, control of breast cancer is likely to significantly affect survival. Variations exist in surgical care, radiotherapy and chemotherapy, depending on age; however, virtually all elderly women with hormone-responsive disease are given adjuvant endocrine therapy, usually tamoxifen. For older women who do not have hormone-responsive cancer, and who have high-risk disease characteristics, questions remain over their best management. Overview data of adjuvant chemotherapy in clinical trials show a significant benefit of chemotherapy for women up to the age of 69 years but, for older women, there are too few data to draw any firm conclusions. When considering treatment options for older women, assessment is critical; functional status and comorbidity are some of the factors linked to shorter survival.

Population-based assessment of hospitalizations for toxicity from chemotherapy in older women with breast cancer.

There are no population-based data on hospitalization rate for toxicity from breast cancer chemotherapy, and even large clinical trials often do not report this information. Medicare data, linked to the Surveillance, Epidemiology, and End-Results (SEER) tumor registries, are now used to assess rates of hospitalization for chemotherapy-related toxicity in a population-based setting. A total of 35,060 women diagnosed with stages I through IV breast cancer aged >or= 65 from 1991 through 1996 were identified from the SEER-Medicare linked program and studied. Patients were defined as being hospitalized for adverse effects of chemotherapy if there was a Medicare inpatient claim for neutropenia, fever, thrombocytopenia, or adverse effect of systemic therapy less than 7 months after diagnosis of breast cancer. More than 9% of women with breast cancer who received chemotherapy were admitted with the diagnosis of neutropenia, fever, thrombocytopenia, or adverse effect of systemic therapy, compared with 0.5% of women with breast cancer who did not receive chemotherapy. The rates for stage I to IV were 6.3%, 8.1%, 12.3%, and 13.2% in those treated with chemotherapy, and 0.4%, 0.6%, 0.7%, and 1.5% in women not treated with chemotherapy. The hospitalization rates for adverse effects increased significantly with comorbidity score and varied more than two-fold across the nine SEER areas but did not vary by age. Use of anthracycline-containing chemotherapy agents was associated with greater odds of these toxicities (eg, odds ratio, 2.53 for neutropenia; 95% confidence interval, 1.97 to 3.26). This study demonstrated the feasibility of using Medicare data to assess rates of hospitalization for serious toxicity associated with cancer chemotherapy. Rates in actual practice were higher than those reported in clinical trials and did not vary by age.

The role of chemotherapy and adjuvant therapy in the management of breast cancer in older women

The management of breast cancer in older women is a major challenge. A meta-analysis of randomized trials of adjuvant therapy in early stage breast cancer has indicated that the use of the antiestrogen tamoxifen improves relapse-free and overall survival for postmenopausal women, including those older than age 70 years. Tamoxifen therapy is of greatest benefit in patients whose primary lesions are estrogen- and progesterone-receptor positive, but lesser yet still significant benefits are seen in receptor-negative patients. Adjuvant chemotherapy has only been minimally studied in older women, because earlier trials tended to exclude women older than age 70 years from protocol entry. Trials are needed to explore the role of adjuvant chemotherapy in older women, especially those older than age 70 years. Metastatic breast cancer is incurable. Standard endocrine and chemotherapy regimens may be of great palliative benefit but probably only have modest effects on prolonging survival; older women should be offered such treatment. Initiating treatment for metastases with endocrine therapy does not compromise survival, even when such therapy is given to women who have receptor-negative malignancy. Patients progressing on endocrine therapy or whose metastatic disease is life-threatening should be considered for chemotherapy. Older women in generally good health tolerate standard doses of chemotherapy as well as their younger counterparts. Future research in this setting should include clinical trials designed specifically for the elderly and should include quality-of-life assessment as a major end point.