2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

Adjuvant Systemic Therapy
Adjuvant systemic therapy refers to the administration of
anticancer therapy after primary breast surgery for early
stage breast cancer with the goal of eradicating occult
micrometastatic disease thought to be responsible for distant
recurrence. Systemic treatment modalities include
endocrine therapy and chemotherapy with or without trastuzumab.
Treatment decision making regarding adjuvant
systemic therapy for older women should involve consideration
of such factors as the risk of morbidity and mortality
from breast cancer, life expectancy and treatment tolerance,
and patient preference. A geriatric assessment that includes
evaluation of functional, cognitive, nutritional, and psychosocial
status, and review of comorbidities and concomitant
medications is particularly helpful in estimating the health
status and life expectancy of older adults. Each of the
components of a geriatric assessment can identify older
adults at increased risk for morbidity and mortality. This
assessment can also identify areas of vulnerability that may
affect the patient’s ability to participate in a treatment plan
(for example, ability to take medications on one’s own).
Items in a geriatric assessment are able to identify older
adults at risk of chemotherapy toxicity. 8,9 In a multisite
study of 500 older adults with cancer, conducted by the
Cancer and Aging Research Group, five geriatric assessment
questions were independent predictors of the risk of chemotherapy
toxicity, in addition to age, tumor, treatment, and
laboratory variables. The geriatric assessment questions
that were predictive of chemotherapy toxicity included hearing
impairment (rated at fair or worse), difficulty in walking
one block, need for assistance with taking medications, one
or more falls in the past 6 months, and decrease in social
activities because of either physical or emotional health. 8
This predictive model for chemotherapy toxicity is being
validated specifically in older adults receiving adjuvant
chemotherapy for breast cancer (clinicaltrials.gov
NCT01472094). In another study of 518 evaluable older
adults with cancer (Chemotherapy Risk Assessment Scale
for High Age Patients), predictors of chemotherapy toxicity
included measures of functional status (ability to complete
4
KEY POINTS
● The undertreatment of older women with breast
cancer has contributed to poorer survival outcomes
for older women than for younger women.
● The principles that guide breast cancer treatment
recommendations for younger and older women are
fundamentally the same.
● Breast cancer treatment decision making should consider
the risk of breast cancer relapse, patient health
status, life expectancy, and patient preference.
● The use of systemic therapy in the adjuvant setting
should be based on tumor characteristics and include
endocrine therapy, and/or chemotherapy with or
without trastuzumab.
● Omission of postoperative radiation therapy is a
reasonable strategy for older women with small
hormone-receptor positive tumors.
instrumental activities of daily living), cognition (Mini-
Mental Status score), and nutrition (Mini-Nutritional Assessment
score). 9 This information can be used in the
treatment decision-making process in order to estimate life
expectancy and risk of chemotherapy side effects and to
identify areas of intervention to assist the patient during her
treatment course.
Endocrine Therapy
OWUSU, HURRIA, AND MUSS
The majority of older patients present with hormone
receptor–positive breast cancer. Endocrine therapy is the
mainstay of adjuvant therapy for these patients and results
in proportional reductions in the risk of relapse and dying
of breast cancer that exceed any available chemotherapy
regimen. Current consensus guidelines recommend adjuvant
systemic endocrine therapy for hormone receptorpositive
breast cancer. The National Comprehensive Center
Network (NCCN) guidelines 10 recommend the use of adjuvant
endocrine therapy for women with hormone receptorpositive
breast cancer regardless of age, menopausal status,
or HER2 status, with the possible exception of women
with lymph node-negative cancers 0.5 cm or less, or 0.6 to
1.0 cm in diameter with favorable prognostic features;
benefit from endocrine therapy is likely to be small for
tumors of this size. In contrast, the St. Gallen International
Consensus Panel recommends adjuvant systemic endocrine
therapy for all women with endocrine-responsive disease
with no exceptions and has defined endocrine-responsive
tumors as those with as few as 1% of cells staining positive
for hormone receptor proteins. 11 The Society of International
Geriatric-Oncology (SIOG) breast cancer task force
recommended that older women with endocrine-responsive
breast cancer be offered systemic endocrine therapy. However,
for women with minimal risk disease, the decision to
offer endocrine therapy should be based on a risk-benefit
analysis. 12
Tamoxifen is the most firmly established adjuvant endocrine
therapy for both premenopausal and postmenopausal
women. Supporting these recommendations are results
from the Early Breast Cancer Trialists’ Collaborative
Group (EBCTCG) overview analysis, which demonstrated
that over a 15-year period, use of adjuvant tamoxifen
therapy for women with known estrogen receptor-positive
disease, compared with no tamoxifen, decreased the 15-year
risk of recurrence and death by 39% and 31%, respectively,
regardless of age. 13 It is clear from these data that
tamoxifen is of benefit for older women. In addition to
decreasing the risk of disease relapse and death, there are
also potential nonbreast cancer benefits of tamoxifen therapy
in postmenopausal women. Tamoxifen may prevent
osteoporosis 14 and reduce the risk of cardiovascular disease.
15 Adjuvant tamoxifen therapy is, however, underutilized
in older women. Women 80 years or older are half as
likely to report having had a discussion about tamoxifen
with their doctor compared with women 65 to 79 years, and
women age 85 to 92 years are 25% less likely to receive a
tamoxifen prescription than those 80 to 84 years. 16 Additionally,
older women are more likely to self-discontinue and
to be nonadherent to tamoxifen before the recommended
treatment period of 5 years, 17,18 undercutting the treatment
benefit from tamoxifen. Oncologists should always ask their
patients if they are taking their prescribed medications and