Hyman B. Muss, MD

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Commentary (Muss): Management of Cancer in the Elderly

February 1st 2006

With the aging of the Western population, cancer in the older person is becoming increasingly common. After considering the relatively brief history of geriatric oncology, this article explores the causes and clinical implications of the association between cancer and aging. Age is a risk factor for cancer due to the duration of carcinogenesis, the vulnerability of aging tissues to environmental carcinogens, and other bodily changes that favor the development and the growth of cancer. Age may also influence cancer biology: Some tumors become more aggressive (ovarian cancer) and others, more indolent (breast cancer) with aging. Aging implies a reduced life expectancy and limited tolerance to stress. A comprehensive geriatric assessment (CGA) indicates which patients are more likely to benefit from cytotoxic treatment. Some physiologic changes (including reduced glomerular filtration rate, increased susceptibility to myelotoxicity, mucositis, and cardiac and neurotoxicity) are common in persons aged 65 years and older. The administration of chemotherapy to older cancer patients involves adjustment of the dose to renal function, prophylactic use of myelopoietic growth factors, maintenance of hemoglobin levels around 12 g/dL, and proper drug selection. Age is not a contraindication to cancer treatment: With appropriate caution, older individuals may benefit from cytotoxic chemotherapy to the same extent as the youngest patients.

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Optimizing Adjuvant Chemotherapy in Early-Stage Breast Cancer

December 1st 2005

Mortality in breast cancer has declined in the past decade, owing toadvances in diagnosis, surgery, radiotherapy, and systemic treatments.Adjuvant chemotherapy has had a major effect on increasing survivalin women with locoregional breast cancer. Like all treatments, adjuvantchemotherapy is a work in progress, and it has evolved from singleoral agents to complex multidrug regimens. The choice of regimens isnot without controversy, however, and several have been shown to bemore effective than others, especially in patients who are at high riskfor recurrence. The taxanes paclitaxel and docetaxel (Taxotere) havebeen shown to be effective in the adjuvant setting, and they have alsobeen shown to improve the outcomes in node-positive disease. Bothdisease-free and overall survival are greater with doxorubicin,paclitaxel, and cyclophosphamide given in a dose-dense, every-2-weekschedule with growth factor support than with the same agents givenin an every-3-week schedule. Disease-free and overall survival in patientswith node-positive disease are greater with docetaxel, doxorubicin(Adriamycin), and cyclophosphamide (TAC) than with fluorouracil,doxorubicin, and cyclophosphamide (FAC). Febrile neutropenia iscommon with the TAC regimen, but it can be minimized with growthfactor support. Based on these findings, dose-dense therapy and TAC arethe current adjuvant treatments of choice in patients with node-positivedisease; other, less-intense regimens may be appropriate in patientswith lower-risk disease. Ongoing trials are investigating the efficacy ofcommonly used regimens, new chemotherapeutic and biologic agents,and novel doses and schedules of currently available agents.

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Selecting Adjuvant Endocrine Therapy for Breast Cancer

December 1st 2004

This year alone, more than 215,000 women in the United States will bediagnosed with, and over 40,000 will die from, invasive breast cancer.Recently, mortality from female breast cancer has declined despite anincrease in its incidence. This decline corresponds with improved screeningfor prompt tumor detection, and advances in the treatment of earlydisease. Of these, endocrine therapy has played a prominent role. Forwomen with estrogen receptor (ER)-positive and/or progesterone receptor(PR)-positive breast cancers, endocrine therapy has proven to be amajor component of adjuvant therapy, but it is not effective in womenwhose breast cancers lack ERs and PRs. The selective estrogen-receptormodulator (SERM) tamoxifen has been well established as safe and effectivein the adjuvant care of both pre- and postmenopausal women withhormone-receptor–positive early breast cancer. For premenopausalwomen, ovarian suppression is an important option to be considered.Additionally, the aromatase inhibitors have recently demonstrated utilityin postmenopausal women. The ideal sequencing of treatment withtamoxifen and/or an aromatase inhibitor is the subject of several ongoingstudies. Factors involved in selecting an appropriate endocrine regimenhave grown considerably over the past decade. It is becoming more importantfor those caring for women with breast cancer to fully understandthe available endocrine treatment options and the prognostic and predictivefactors available to help select the most appropriate treatment. Thegoal of this article is to assist clinicians in making decisions regardingadjuvant hormonal therapy and to provide information regarding availableclinical trials. To achieve this, the therapeutic options for hormonaltherapy will be reviewed, as will prognostic and predictive factors used inmaking decisions. Finally, four cases illustrating these difficult decisionswill be discussed, with recommendations for treatment.

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Systemic Therapy for Older Women With Breast Cancer

March 1st 2001

Breast cancer is a common problem in older women. As the number of medical illnesses increases with age and the life expectancy decreases, the benefits of systemic therapy for women with breast cancer become questionable. All women over age 65 years are at high enough risk of breast cancer to consider the risk/benefit ratio of preventive therapy with tamoxifen (Nolvadex) or participation in the Study of Tamoxifen and Raloxifene (STAR) trial. Adjuvant chemotherapy and hormonal therapies for early breast cancer significantly improve disease-free and overall survival; recommendations for their use are based on risk of tumor recurrence. Use of tamoxifen in the adjuvant setting in women with receptor-positive tumors is a relatively simple decision in light of its favorable toxicity profile. The delivery of adjuvant chemotherapy is a more complicated decision, and the patient’s wishes, estimated life expectancy, presence of comorbid conditions, and estimated benefit from treatment should be considered. The primary goal of the treatment of metastatic breast cancer is palliation. We discuss trials specific to older women and make appropriate treatment recommendations. Unfortunately, there is a paucity of data from clinical trials in women over age 70 years. However, because the clinical trial is the primary scientific mechanism for testing the efficacy of a treatment, every effort should be made to enter older women into treatment protocols. [ONCOLOGY 15(3):280-299, 2001]