WOMEN'S HEALTH
could safely be treated with endocrine therapy alone.
There are many theories as to why this disparity of outcome
with age. The genomic assay should reflect the biology of the tu-
mor itself and thus should not be impacted by age. Could there
be host factors which account for the difference? Is it possible the
differences are due to the indirect effects of chemotherapy such as
chemotherapy-induced amenorrhea? More trials are needed to
better understand premenopausal breast cancer so that treatment
can be better tailored for this subgroup.
In fact, although we have been able to de-escalate breast cancer
treatment broadly, for the premenopausal group, especially the very
young (defined as less than 35-years-old) treatment advances have
only escalated therapy. While the mortality rate for breast cancer
overall has steadily declined, the mortality rate for young women has
remained constant. Other than injury, cancer remains the leading
cause of death for American women under the age of 40 and breast
cancer is the leading cause of cancer death in women aged 25-40 in
the US (3,8,9). Similarly, although the incidence of breast cancer in
older women is on the decline (thought largely due to the decline in
use of hormone replacement therapy,) the incidence of breast cancer
in younger females has remained steady for the last 30 years. Most
alarming is that women age < 40 experience nearly one and a half
to two times the risk of death compared to older patients with the
same disease subtype (4).
This disparity is often attributed to known prognostic factors
such as stage and lymph node status. Younger women are more likely
to be diagnosed at a later stage with symptomatic disease based on
lack of screening use and early detection in this age group. However,
age remains an independent risk factor for poor prognosis. Although
young age is more likely to be associated with family history, genetic
mutation and triple negative subtype, the majority of young women
with breast cancer will not have a family history or gene mutation.
Estrogen positive breast cancer remains the most common breast
cancer diagnosed in this age group (4).
Several treatment related factors also influence outcome. For
example, the role of ovarian suppression in premenopausal women
has only recently become standard of care in high-risk young women
based on the SOFT and TEXT trials. Ovarian suppression plus an
aromatase inhibitor demonstrated a risk reduction of 28 percent
compared to tamoxifen alone. This benefit was most pronounced
in the very young (less than 35-years-old) likely based on lower
rates of chemotherapy-induced amenorrhea in this age group (5,
6), thus prompting the hypothesis for the contrasting outcome in
the TAILORX trial noted above.
Secondly, adherence to adjuvant endocrine therapy is also a
particular problem in this age group, as menopausal side effects are
most pronounced and negatively impact quality of life. This is mag-
nified by the addition of ovarian suppression. Hot flashes, depression
and osteoporosis are well-described complications of antiestrogens
for all age groups. However, in the very young, complications such
as cognitive function, body image and sexual dysfunction are more
pronounced (7). Fertility is also a major concern for this age group,
especially as the treatment duration of endocrine therapy length-
ens; family planning remains a challenge to compliance. Although
pregnancy itself is safe after a breast cancer diagnosis, the safety of
interrupting endocrine therapy to allow for pregnancy is unknown.
Current trials are underway to address this question.
These treatment and survivorship issues complicate the care of
young women with breast cancer. In some cases, our interventions
provide only marginal benefit at a significant personal cost. Mul-
tidisciplinary discussions must occur to coordinate care for these
women to preserve family planning options, cognitive and sexual
functioning in the setting of curative treatment options, so that
these women may have the best chance to lead full personal and
professional lives. It was this need that led to the establishment of
the HER Program for young women with breast cancer at the James
Graham Brown Cancer Center. This program aligns specialists in
reproductive endocrinology, oncoplastic surgery and oncology,
among other specialties, with women 45 or younger diagnosed with
breast cancer in our region. The goal of the HER program is to rec-
ognize and address these issues both clinically and from a research
perspective. We hope this effort, along with better research will
narrow the outcome gap for these women, and the mortality decline
will continue for women of all ages diagnosed with breast cancer.
References
1. Sparano, JA et al Adjuvant Chemotherapy Guided by a 21 Gene
Expression Assay in Breast Cancer. NEJM 2018; 379:111-121
2. http://www.ascopost.com/News/58904
3. National Cancer Institute. Surveillance, Epidemiology and End
Results Program (SEER) Cancer Statistics, 2016
4. Freedman et al. Emerging Data and Current Challenges for
Young, old, obese or male patients with breast cancer. Clin
Cancer Res; 23(11) June 1, 2017
5. Francis, PA et al, Adjuvant ovarian suppression in premeno-
pausal breast cancer, NEJM 2015; 372: 436-46
6. Pagani O et al. Adjuvant exemestane with ovarian suppression
in premenopausal breast cancer. N Eng J of Med 2014/ 371:
107-108
7. Partridge et al Non adherence to adjuvant tamoxifen therapy
in women with primary breast cancer.
8. https://www.cdc.gov/women/lcod/2015/all-females/index.htm
9. https://seer.cancer.gov/statfacts/html/breast.html
Dr. Riley is as associate professor of medicine at the University of
Louisville and Deputy Director of Clinical Affairs at the James Graham
Brown Cancer Center.
OCTOBER 2018
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