2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Adjuvant Therapy for Older Women with
Early-Stage Breast Cancer: Treatment
Selection in a Complex Population
By Cynthia Owusu, MD, MS, Arti Hurria, MD, and Hyman Muss, MD
Overview: Breast cancer is a disease of aging. However,
older women with breast cancer are less likely to participate in
clinical trials or to receive recommended treatment. This
undertreatment has contributed to a lag in breast cancer
survival outcomes for older women compared with that for
their younger counterparts. The principles that govern recommendations
for adjuvant treatment of breast cancer are the
same for younger and older women. Systemic adjuvant treatment
recommendations should be offered on the basis of
tumor characteristics that divide patients into three distinct
subgroups. These include (1) older women with hormone
receptor (HR)-positive and human epidermal growth factor 2
(HER2)-negative breast cancer who should be offered endocrine
therapy; (2) older women with HR-negative and HER2negative
breast cancer who should be offered adjuvant
BREAST CANCER is the most common cancer in American
women and the second leading cause of cancerrelated
deaths among women. In 2011, approximately
230,480 new cases were diagnosed in the United States,
with an expected 39,520 deaths. 1,2 The most important risk
factor for breast cancer is age. The estimated lifetime risk of
a new breast cancer is 1 in 15, 1 in 29, 1 in 27 and 1 in 207
for women 70 years or older, 60 to 69, 40 to 59, and 39 or
younger, respectively. 1 The median age at the time of breast
cancer diagnosis is currently 61 years and an estimated 45%
of women are 65 or older at the time of initial diagnosis. 2,3
Recent gains in life expectancy, coupled with aging as a risk
factor for breast cancer, makes breast cancer primarily a
disease of older women, with increasing public health importance.
In 1980, persons 65 and older represented 11.3%
of the total population, but by 2030 this proportion is
expected to increase to 20%. 3 In addition, by 2030, persons
older than 75 will be expected to account for just under 50%
of the total cohort older than 65. 4 Given the nonlinear
age-risk relationship and increasing life expectancy, a substantial
proportion of older women are expected to be affected
by breast cancer.
Age-Related Cancer Health Disparities
Evaluation of the biology of breast cancer by patient age
has shown that hormone receptor-positive, low S-phase, low
tumor grade and HER2-negative tumors are more common
among older than younger women, 5 although these differences
are relatively modest. Despite the favorable tumor
profile of breast cancer in older women, this has not translated
into any major survival advantage for older women
with breast cancer in comparison with their younger counterparts.
In a study that drew data from National Vital
Statistics Reports and the Surveillance Epidemiology and
End Results database of the National Cancer Institute,
Smith and colleagues 6 found that although the rate of breast
cancer death in the general population and the adjusted risk
of death among women with newly diagnosed disease are
declining among all age groups, the least decline has been
among older women. Relative to 1990, the rate of breast
chemotherapy; and (3) older women with HER2-positive disease
who should be offered chemotherapy with trastuzumab.
Exceptions to these guidelines may be made for older women
with small node-negative tumors or frail older women with
limited life expectancy, where close surveillance may be a
reasonable alternative. Addressing the current age-related
disparities in breast cancer survival will require that older
women are offered the same state-of-the-art-treatment as
their younger counterparts, with a careful weighing of the
risks and benefits of each treatment in the context of the
individual’s preferences. In addition, older women should be
encouraged to participate in breast cancer clinical trials to
generate additional chemotherapy efficacy, toxicity, and quality
of life data.
cancer death in the general population decreased 2.5% per
year for women age 20 to 49, 2.1% per year for those age 50
to 64, 2% per year for those age 65 to 74, but 1.1% per year
for those age 75 years and older. Moreover, among women
with newly diagnosed breast cancer between 1980 and 1997,
the adjusted risk of death decreased by 3.6% per year among
women younger than age 75 compared with 1.3% per year
among those age 75 and older (p � 0.01). These differences
were even greater for older black women. The age-related
disparity in survival outcomes was hypothesized to be related
to the undertreatment of older women with breast
cancer. In an analysis of 9,766 patients enrolled in the
TEAM (Tamoxifen Exemestane Adjuvant Multinational)
randomized controlled trial conducted with postmenopausal
women with hormone receptor-positive breast cancer, increasing
age was associated with a higher disease-specific
mortality. 7 Treatments received and tumor characteristics
did not completely explain the age-related differences in
survival outcomes but older patients in this trial were much
less likely to receive chemotherapy. Together, these data
clearly underscore the fact that breast cancer is an important
disease of older women who bear a disproportionate
burden of the morbidity and mortality associated with the
disease and who should be offered proven treatments that
improve survival outcomes. Given that treatment differences
do not completely explain the age-related disparities
in survival outcomes, additional population and translational
studies are needed to provide further insight into the
reasons for these disparities.
From the Case Western Reserve University School of Medicine, Cleveland, OH; City of
Hope Medical Center and Beckman Research Institute, Duarte, CA; and, Lineberger
Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC.
Authors’ disclosures of potential conflicts of interest are found at the end of this article.
Address reprint requests to Cynthia Owusu, MD, MS, Case Western Reserve University
School of Medicine, Division of Hematology/Oncology and Case Comprehensive Cancer
Center-BHC 5055, 11100 Euclid Avenue, Cleveland, OH 44106; e-mail: cynthia.owusu@
case.edu.
© 2012 by American Society of Clinical Oncology.
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