MAJOR RISK FACTORS AFFECTING TRIPPLE NEGATIVE

BREAST CANCER IN BLACK WOMEN

By Antonette Grandison

JULY 25, 2018

THE OHIO STATE UNIVERSITY
Introduction
Breast Cancer incidence affects women more than any other cancer. A large number of
cases per year has resulted in well-developed research that has led to therapies which have
increased survival rates and decrease mortality rates. Like other cancers, breast cancers can be
divided into many different subtypes. The luminal A-like subtype is the most prevalent and
encompasses estrogen receptor positive (ER+) and or progesterone receptor positive (PR+),
HER2-positive (HER2+). Subtype A has targeted therapies that have been developed and results
in higher cure rates. As a result, the most common factors that determine the risk for a woman
having breast cancer are based on subtype A.

On the other hand, triple negative breast cancer (TNBC) has a much lower incidence
overall and doesn’t have conclusive targeted therapies. This subtype is negative for ER, PR, and
Her-2. Furthermore, TNBC has a higher incidence in black women than in white women and
current research has not yet identified the cause. Current research has mostly examined the
molecular elements that result in the diagnosis of TNBC. But, the results of this research have
not been analyzed to determine if new independent risk factors need to be used for predicting the
risk of triple negative breast cancer. More specifically, if separate risk factors need to be
allocated for black women since they exhibited the highest rate of being diagnosed with TNBC.
Once the factors are better identified, the next step will be evaluating if risk factors for black
women should be re-evaluated to decrease the incidence. Also, by addressing the higher
incidence of triple-negative breast cancer, this may impact the stage at which black women are
being diagnosed increasing survival rates and decreasing mortality rates. My study will examine
if better risk factors can be identified for detecting triple-negative breast cancer in black women
allowing practitioners to better equipped to asses and diagnose this subtype in black women.

Hypothesis
My research topic will be to examine the risk factors that affect the hormones of triple
negative breast cancer. Since TNBC has a higher incidence in black women than in white
women, I want to research the specific risk factors that differ in white and black women that lead
to the increased incidence. Once better descriptive risk factors are identified, the next step will be
investigating if risk factors for black women should be re-evaluated to better predict the

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probability of black women developing TNBC. Also, by addressing the higher incidence of
triple-negative breast cancer, this may also impact the stage at which black women are being
diagnosed leading to increased survival rates and decreased mortality rates. My hypothesis will
be that if there are better risk factors for detecting TNBC in black women then diagnoses will
happen at earlier stages because the risk factors are better targeted for predicting vulnerable
populations.

Literature Review
Bertrand et al. state that black women have a 70% higher incidence of developing the
most aggressive Basal-like subtypes leading to higher mortality rates.3 Basal-like subtype
cancers are more aggressive, higher in histological grade, and have a high proliferative index all
resulting in a worse prognosis.11 TNBC has been identified as having a higher frequency of P53
mutations along with the Rb1 gene.11 Neophytou and colleagues suggest that TNBC is caused by
deregulation of adult mammary stem cells during tumorigenesis causing disruption of the
luminal progenitor cells.11 This leads to a buildup of mutations and the eventual development of
TNBC. Bertrand et al used a large prospective cohort study which included black women only.
The results found that higher birth age at first birth, never breastfeeding, greater adiposity of the
abdomen, and waist to hip ratio was found to be important risk factors for developing ER-
subtype breast cancer. 3 The large sample size helps emphasize the significant differences and
show that black women have rates of higher parity and greater abdominal adiposity. But lower
rates of breastfeeding leading to the difference between black and white women were not
explored further because white women were not included in this study. The risk factors must be
compared between the two groups to determine if separate risk factors exist and if they would
benefit practitioners if used.

Jones and Chilton pose questions for further investigation addressing what factors could
be changed or added to better estimate risk among black women? If the model is changed
clarification will need to be made if the new model needs to be created to address biological
measures.8 The questions posed were helpful in directing research, but their methods and results
did not provide significant evidence. The researchers address that more adequate and consistent
cancer data for black women would improve the results of their study. Also, the researchers

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noted that previous models and research are a better predictor for women who have consistent
access to annual mammograms.

Past research has identified estrogen receptor (ER), progesterone receptor (PR) and
human epidermal growth factor receptor-2 (HER2) as receptors that influences the subtype of
breast cancer and as a result can impact the survival and mortality rates. TNBC is the result of
ER-, PR- and HER2-. TNBC is the second most common subtype of breast cancer and accounts
for 10-25% of the invasive cases. It is second only to subtype luminal A which occurs in 62-67%
of cases. 10 The incidence of TNBC is much higher in young women or premenopausal women
and in African American women. As the most common subtype, the luminal A subtype has
targeted therapies that aid in the treatment of this subgroup. In contrast, there currently is no
targeted therapy for TNBC. The risk factors for TNBC are fairly unknown as well as what
hormonal factors or race factors may affect it. Previous studies have evaluated some of the major
reproductive factors and their effect on the ER/PR/HER-2 hormones and their eventual influence
on the development of breast cancer.10 Ma and colleagues only included women in their study
who had previously been involved in previous studies. By including women with prior
participation limits the external validity of the research results by concentrating on a specific
demographic. An advantage of this study is the fact that they did compare white women and
black women with breast cancer to a control group which included women who have had no
history of invasive breast cancer.10 Ma and colleagues found that duration of breastfeeding can
lower the chance of TNBC, especially in young black women. Breastfeeding decreases the risk
of ER-/PR- and thus the overall risk of TNBC. 10 But data was inconclusive if race impacted the
relationship between breastfeeding. Race and/or genetic susceptibility may both be factors in
causing the increase in incidence. The size of participants overall was appropriate, but groups
were not distributed evenly which again makes the data harder to translate and could possibly
skew the data. Also, 36% of the participants included in the study were missing information on at
least one of the gene receptors.

By a percentage of participants missing receptor information, this does not provide an

appropriate distribution for subtypes. Molecular subtypes of breast cancer relate to tumor marker
expression and gene expression having different clinical profiles and outcomes. 4 Chen and
colleagues separated participants based on ER/PR/HER-2 status. Those without receptor

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information were excluded.4 This study concluded that differences did exist between several
reproductive factors and different subtypes. They also found that the later age at first birth is also
an associated factor with some groups.4 The researchers state that the biological mechanisms that
are responsible for the relationships between subtypes, expression, and race need to be
investigated.4 The additional effect of breastfeeding on TNBC should also be further
investigated. 4 Breast cancer is considered a heterogeneous disease and TNBC has different
molecular characteristics and may result in different etiologies.2 Little research has been done on
the interaction of alcohol consumption and smoking on impacting the risk of TNBC. Baglia and
colleagues allocated participants by receptor status but did not further separate them into
subdivided groups comparing black and white women. Also, this study took participants that
either had TNBC or H2E and not exclusively TNBC. Smoking is a multitiered factor and may be
the cause of several factors and not just one. Therefore, it is difficult to separate which factor is
the true cause for TNBC when using multitiered factors. But this study determined again that
there is evidence that breast cancer etiology can differ based on subtype. 2

Methods
This study utilized services from hospitals in the Columbus area, including The James,
Stephanie Spelman Breast Cancer center, Riverside hospital, Mt Carmel East and West, and
Dublin Methodist Hospital. The population pooled from these locations will be women who have
already been diagnosed with invasive breast cancer. At the time of consultation with the
physician, the women will be asked to participate in the study and if they agree, they will be
given the risk factor survey detailed in Figure 1. If a complete list of risk factors cannot be
obtained from the survey at the consent of the participant their medical health records will be
examined. This study will sample women between the ages of 29 to 69 years old that have been
diagnosed with invasive breast cancer in the in Ohio over a period of 5 years. The cases in this
study will include only white and black women forming two distinct groups. Pathology reports
were completed for each woman if they were not obtained previously. Then, the pathology
reports were used to further divide the women into subgroups based on ER/PR/HER status. The
subgroups will consist of luminal A (ER+/HER2-), luminal B (ER+/HER2+), and TNBC (ER-
/PR-/HER2-). Any other tumor markers will not be included in this study. Also, to eliminate the
confounding variable of smoking and alcohol consumption, participants with these habits will be

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matched. For example, a white woman, who smokes and consumes alcohol will be compared
with a black woman who also smokes and consumes a similar amount of alcohol. Once all data
has been collected, results will be analyzed, and risk factors will be compared for each subgroup.
The risk factors will be tabulated based on race, ER/PR/HER status, age, demographic factors,
reproductive factors, epidemiologic factors, behavioral factors and lifestyle factors.

Discussion
After collecting all the risk factor forms, the data was tabulated based on the information
given by each participant (Figure 2). If the hypothesis is accepted, I would expect there to be a
greater number of black women diagnosed with TNBC. Also, when compared to white women I
would expect at a minimum one risk factor will be present in black women with a higher
frequency (Figure 3). The difference in frequency may be seen in black in general as well as
black women with TNBC. If the hypothesis is rejected, I would expect to see a similar
distribution of all risk factors for both black and white women (Figure 4). Similarly, if the
hypothesis would be rejected if there was a similar distribution for all women that have been
diagnosed with TNBC.

Implications for future research would affect several modalities in oncology including
methods for detection of invasive breast cancer as well as improved preventative measures. If
risk factors can be modified based on ethnicity or any other factors, treatment and diagnoses
could be better tailored for each patient. The result would hopefully increase survival rates and
decreased survival rates for all women with invasive breast cancer. This study is building upon
the foundation set by the studies discussed previously by further examining the nuances between
ER/PR/HER status and the factors that affect them but going further by comparing them amongst
black and white women.

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Figures

Figure 1. Risk Factor Assessment Sheet

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Figure 2. Risk Factor Data Table

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Figure 2 (continued).

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Figure 3.

Figure 3. Incidence of different receptor subtypes based on hip circumference between white
and black woman.

Figure 4.

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Figure 4. Incidence of different receptor subtypes based on hip circumference between white and
black woman.

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