2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

TREATMENT FOR OLDER WOMEN WITH BREAST CANCER
Endocrine-positive,
HER2-negative
Endocrine-negative,
HER2-negative
Table 1. Summary of Recommendations for Adjuvant Systemic Therapy in Early Stage Breast Cancer in Older Women
patients younger than 65. Regardless, in the absence of
contraindications, trastuzumab is currently recommended
for the adjuvant treatment of HER2-positive breast cancer,
even for older women. In older women, a nonanthracycline,
trastuzumab-containing regimen of TCH is often used because
of the increased risk of cardiotoxicity associated with
the anthracycline and trastuzumab regimen.
In summary, the principles that govern recommendations
for systemic adjuvant treatment of breast cancer are the
same for younger and older women. Older women should
be offered guideline-recommended therapies (Table 1).
Broadly, these recommendations should be offered along
three clinically distinct subgroups based on tumor characteristics.
(1) Older women with hormone receptor-positive
and HER2-negative breast cancer who should be offered
endocrine therapy regardless of node status. Gene expression
profiling assay may be used to determine the added
benefit of chemotherapy for those with node-negative
disease; (2) older women with hormone receptor–negative
and HER2-negative breast cancer (triple-negative breast
cancer) who should be offered adjuvant chemotherapy; and
(3) older women with HER2-positive disease who should
be offered chemotherapy with trastuzumab. In the last
group, women with hormone receptor-positive tumors
should also be offered endocrine therapy. Exceptions to
these guidelines may be made for older women in any of the
three subgroups who have node-negative disease and a
tumor less than 1 cm or for frail older women with limited
life expectancy, where close surveillance may be a reasonable
alternative.
Adjuvant Radiation Therapy
Node-negative,
Tumor size � 1cm
No adjuvant therapy or
Consider hormonal therapy if tumor size � 0.6 cm,
grade 2, or other high risk features
No adjuvant therapy or
Consider chemotherapy if tumor size � 0.6 cm plus
other high risk features
HER2-positive No adjuvant therapy or
Consider chemotherapy with trastuzumab if tumor
size � 0.6 cm plus high risk features
Until recently, the guideline recommendation, regardless
of age, was for all women to receive radiation therapy
after breast-conserving surgery and for postmastectomy
radiation to be offered to women with a high probability of
local recurrence. A recent meta-analysis of the EBCTCG
supports these recommendations, showing that radiation
therapy decreased the 10-year risk of any first recurrence
from 35% to 19% and the 15-year risk of breast cancer death
from 25% to 21% among women treated with breastconserving
surgery. 40 Although the proportional reductions
in relapse were similar among all women, the absolute
benefits varied substantially by age, grade, estrogen receptor
status, tamoxifen use, and extent of surgery. The authors
concluded that radiation therapy after breast-conserving
surgery halves the rate at which the disease recurs and
reduces the breast cancer death rate by about a sixth.
However, older women with small tumors can be spared
radiation therapy. In a landmark randomized controlled
study by Hughes and colleagues 41,42 636 women 70 or older
who had undergone lumpectomy for stage I hormone
receptor-positive breast cancer were randomly assigned to
receive either radiation therapy and adjuvant tamoxifen
for 5 years or to adjuvant tamoxifen for 5 years alone. The
results demonstrated no substantial differences between
the two groups with regard to mastectomy rates for local
recurrence, distant metastases, or overall survival (median
follow-up of 12 years). Of the 49% of patients who died
during follow-up, 3% died of breast cancer. The only statistically
significant difference was found in the rate of local
or regional recurrence at 5 years, (2% among women who
had radiation therapy compared with 9% who did not).
Based on results from this study, one may reasonably
consider lumpectomy (with surgically clear margins)
without radiation therapy for women 70 and older with
clinically negative lymph nodes, a tumor 2 cm or smaller,
and hormone receptor-positive breast cancer who agree
to take endocrine therapy. This strategy is limited by the
high rate of nonadherence and early discontinuation of
adjuvant systemic endocrine therapy among older
women. 43,44 Omission of postoperative radiation therapy,
coupled with nonadherence to adjuvant systemic endocrine
therapy, may result in earlier recurrences and, ultimately,
poorer survival outcomes for older women. A favorable
outcome from this approach can be achieved only when
older women are adherent to prescribed oral endocrine
therapies. Adherence to prescribed endocrine therapy
should therefore be discussed and encouraged at follow-up
visits.
Conclusion
Node-negative,
Tumor size � 1 cm Node-positive
Hormonal therapy
Consider chemotherapy based on geneexpression
profiling results
Hormonal therapy
Chemotherapy
Chemotherapy alone Chemotherapy alone
Chemotherapy with trastuzumab
Add hormonal therapy if hormone
positive
Chemotherapy with trastuzumab
Add hormonal therapy
if hormone positive
Breast cancer is a disease of aging. With minor differences,
existing data support similar recommendations for
both younger and older women. However, there are agerelated
differences in treatment patterns, with older women
less likely than younger women to receive standard therapies.
Furthermore, survival outcomes lag behind that of
younger women. Closing the current gap in age-related
disparities in breast cancer survival will require that
older women are offered the same state-of-the-art treatment
as younger women, with a careful weighing of the risks
and benefits of each treatment in the context of the individual’s
preferences. Newer tools that estimate life
expectancy and toxicity as well as the potential benefits of
therapy should make it easier for oncologists to make better
treatment decisions with older patients. In addition, older
women should be encouraged to participate in breast cancer
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