Hyman B. Muss, MD

In this review, we will discuss the role of geriatric assessment, alternative treatment modalities for older women with triple-negative breast cancer, and other special considerations for this patient population.

This video examines challenges and opportunities in getting older patients with cancer enrolled in clinical trials.

In this interview, Dr. Hyman Muss discusses some of the barriers to providing high-quality care to geriatric cancer patients, including the barriers to diagnosis and treatment.

Can knowledge of a patient’s breast tumor genome help select the optimal treatment, and when we have an effective treatment for a group of patients-in this case, for breast cancer patients in the adjuvant setting-how long should the course of treatment be?

In this review we will discuss how to evaluate older breast cancer patients, including estimating survival, defining functional limitations, and providing guidelines for optimal adjuvant therapies.

Dr. Balducci has presented a timely and useful overview of bone health in elderly patients undergoing cancer treatment. This topic has important implications, not only within geriatric oncology but also throughout the entire age spectrum. Dr. Balducci’s focus on the elderly population is especially relevant, as this group is at particularly high risk for bone complications over the course of cancer therapy. In his review, Dr. Balducci provides an introduction to the physiology of bone reabsorption and formation, and discusses risk factors for the interruptions in usual physiologic homestasis that lead to osteoporosis.

Although increasing age is the major risk factor for breast cancer incidence and mortality, when adjusted for disease stage, breast cancer mortality is similar among younger vs older patients. Importantly, about 90% of older women with breast cancer present with early-stage disease. The biologic characteristics of breast tumors in older patients suggest they would derive benefit from adjuvant therapy, particularly endocrine therapy, but older women are still frequently undertreated, resulting in poorer survival. Studies suggest that focusing on comorbidity rather than “chronologic age” as a surrogate for life-expectancy is a key aspect of adjuvant decision-making for older patients. Morbidity and mortality from cancer in vulnerable patients with poorer health can be accurately predicted by the Comprehensive Geriatric Assessment (CGA), which evaluates comorbidities, functional status, cognition, social support, psychological state, nutritional status, and polypharmacy. Use of the CGA and newer versions of this tool can lead to interventions that maintain function and improve quality of life in older patients with breast cancer.

By the year 2030 most patients with breast cancer will be aged 65 years or more and many will be frail. Frailty implies diminished physiologic reserve; contributors include diminished organ function, comorbidities, impaired physical function, and geriatric syndromes. Time-efficient tools for assessing frailty are being developed and, once validated, can be used to identify frail cancer patients and help direct therapy. Screening mammography in frail patients is questionable, and a clinical breast exam is likely to identify breast cancers that warrant intervention. Hormonal therapy may be a reasonable primary therapy in older frail women with hormone receptor–positive lesions. For estrogen receptor– and progesterone receptor–negative lesions, excision of the primary tumor may be adequate. Adjuvant hormonal therapy may be appropriate in frail elders with high-risk hormone receptor–positive breast cancer; chemotherapy is rarely indicated regardless of tumor status. The majority of frail elders with metastases will have hormone receptor–positive breast cancers, and endocrine therapy should be considered; those with receptor-negative tumors may be treated with single-agent chemotherapy or supportive care measures. Oncologists need to acquire the skills to appropriately identify frail elders so they select appropriate therapies that will minimize toxicity and maintain quality of life.

As the aging population in the United States continues to grow, the incidence of diseases of the elderly, such as breast cancer, are increasing. Many more elderly women are expected to be diagnosed with new breast cancers, most of them in an early stage. Appropriate treatment of these women is important, as they have poorer outcomes when undertreated. In this review, we will discuss the biology and treatment of early breast cancer in elderly women. We will focus on the role of comorbidity and its effect on life expectancy, treatment decisions, current recommendations for primary treatment with surgery, radiation and neoadjuvant strategies, and adjuvant treatment including local radiation therapy and systemic treatment with endocrine therapy, chemotherapy, and newer agents. Finally we will discuss the importance of clinical trials in the elderly.

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.

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.

Even now, cancer is a disease ofaging; the average age of a newlydiagnosed cancer patient inthe United States is greater than 65years. Safe and effective medical carefor the elderly will become an increasinglyimportant issue as our populationages over the next severaldecades. By 2025, 20% of the USpopulation will be over the age of 65.It will be essential for physicians tobe well versed in assessing and treatingpatients in this age group in a mannerappropriate to their unique medicalneeds. As the population ages, and bettertreatment for other diseases contributesto longer life expectancy, theassessment and treatment of cancer inthe elderly will be an increasingly commonproblem for oncologists.

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.

The authors present a comprehensivereview of anthracycline-based adjuvant chemotherapyregimens, supporting the useof these regimens over CMF (cyclophosphamide[Cytoxan, Neosar],methotrexate, fluorouracil [5-FU]) inearly-stage breast cancer. They concludethat the addition of taxanes toanthracycline-containing regimens innode-positive disease may conferadditional benefit. Newer regimenscontaining taxanes and other agentsthat omit the use of anthracyclinesshow promise but are still underinvestigation.

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]

In 1999, metastatic breast cancer claimed the lives of almost 45,000 women. For the vast majority of patients, metastatic breast cancer is an incurable disease with a median survival of only 2 to 3 years after diagnosis. The

We agree with Drs. Fennelly and Schneider that data from prior clinical trials performed in patients with suboptimally debulked ovarian cancer indicate that increasing the dose intensity of cisplatin (Platinol) does not translate into meaningfully higher response rates, longer response durations, or improved survival. The Gynecologic Oncology Group study is most persuasive in showing that doubling the standard dose of cisplatin and cyclophosphamide (Cytoxan, Neosar) while delivering the same total dose does not improve outcome [1].

Hormonal manipulation is currently the mainstay of palliative care for metastatic breast cancer because it is well tolerated and produces significant responses in approximately one-third of unselected patients. Tamoxifen, a nonsteroidal antiestrogen, is currently considered first-line therapy. Second-line agents include progestins and aromatase inhibitors.

Tamoxifen (Nolvadex) is widely used in the treatment of breast cancer. It is effective in the management of both early stage and advanced disease. The recent comprehensive meta-analysis of systemic treatment in early breast cancer reported that tamoxifen reduced the annual odds of breast cancer recurrence by 25%, and the risk of death by 16%, compared with patients not treated with tamoxifen [1]. The benefits are even more pronounced in postmenopausal patients, with 29% decreases in recurrence and 20% reduction in the risk of death. The risk of contralateral primary breast cancer is also decreased by approximately 28% in women receiving adjuvant tamoxifen [2]. This has prompted its use in prevention trials; the National Surgical Adjuvant Breast and Bowel Project Prevention trial (NSABP P1) is an ongoing trial randomizing women at high risk for breast cancer to receive tamoxifen or placebo. Tamoxifen's use in otherwise healthy women has brought attention to the few potential toxicities of the drug.