In this webinar, Dr. Onyinye D. Balogun and Dr. Lisa Newman of Weill Cornell Medicine-New York Presbyterian Hospital Network discuss all aspects of triple negative breast cancer and its impact on women of color in recognition of Black History Month.

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Triple Negative Breast Cancer and
Women of Color
Lisa A. Newman, MD, MPH, FACS, FASCO
Weill Cornell Medicine/New York Presbyterian Hospital Network
Director, Interdisciplinary Breast Oncology Program
Director, International Center for the Study of Breast Cancer Subtypes
Adjunct Professor, M.D. Anderson Cancer Center
Adjunct Professor, University of Michigan
SHARE Cancer Support

2. Good News:
Overall Declining Breast Cancer Mortality Rates!

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4. Breast Cancer Screening
• EARLY DETECTION SAVES LIVES!!!!
• Advantages to catching breast cancer early:
– Improves chances of successful treatment with
breast-saving surgery
– For women undergoing mastectomy, increases
likelihood of successful breast reconstruction
– Reduces likelihood of needing chemotherapy
– Reduces likelihood of needing extensive lymph
node surgery

5. Breast Cancer Burden of
African American Compared to
White American Women
• Socioeconomic
Disparities
• Tumor biology
• Genetics
• Lifestyle &
Reproductive
Experiences
• Environmental
exposures
• Diet/Nutrition
• Higher mortality rate
• More advanced stage
distribution
• Younger age distribution
• Increased risk of adverse tumor
features
• Higher incidence of male breast
cancer

6. SOCIOECONOMIC DISPARITIES
11.60%
8.20%
3.30%
25.80%
11.90%
6.50%
PROPORTION LIVING BELOW
POVERTY LEVEL
PROPORTION UNINSURED PROPORTION UNEMPLOYED, AGE
>19 YEARS
White Americans African Americans
Sources: U.S. Census Bureau 2013
National Center for Health Statistics/DHHS 2015
US Department of Labor Statistics 2017

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8. Delivery of Care Disparities:
Effect of Race/Gender on ER Evaluations
• 720 physicians viewed
patient interviews
– Professional actors
• Reviewed data regarding
hypothetical patient
• The physicians then
made recommendations
regarding follow-up care
New England J of Medicine, 1998

9. Delivery of Care Disparities:
Breast Reconstruction at M.D. Anderson
Tseng et al, Cancer 2004
Odds
Ratio
African
American
compared to
White American
mastectomy
patients
Referral to
Plastic Surgeon
0.52
Reconstruction
Offered
0.35
Reconstruction
Performed
0.50

10. INADEQUATE DIVERSITY IN THE
HEALTHCARE WORKFORCE
0%
2%
4%
6%
8%
10%
12%
14%
African Americans Hispanic/Latino
Americans
General Population
Physicians (AMA)
Surgeons (ACS)
American College of Surgeons
Oncology Group

11. SO……
Since well-documented
socioeconomic factors explain
many race/ethnicity-associated
breast cancer disparities…

12. Why should we invest in research to
study race/ethnicity-associated
variations in the biology and/or
pathogenesis of breast cancer?

13. SES-Adjusted Meta-Analysis, 2006
>13K AA & 75K WA Breast CA Pts; 19 Studies
mortality hazard
.1 .5 1 5 10
Combined
Crowe
Jatoi 1995-99
Bradley
Polednak
Albain Postmen
Albain Premen
Roetzheim
El Tamer
Yood
Wojcik
Howard
Franzini
Simon (<50 yo)
Simon (>49 yo)
Perkins
Eley
Neale
Ansell
Gordon
Coates
Bassett
AA Mortality Risk: 1.28 (95% CI 1.18-1.38)
Newman et al, JCO 2006

14. Breast Cancer Burden of
African Americans Compared to White Americans
• Socioeconomic
Disparities
• Delivery of
Care
• Tumor biology
• Genetics
• Lifestyle &
Reproductive
Experiences
• Environmental
exposures
• Diet/Nutrition
• Higher mortality
• Advanced stage distribution
• Younger age distribution
40% AA pts <50 years old
20% WA pts <50 years old
•Higher risk of adverse tumor features
•Higher incidence Triple Negative and
Inflammatory Breast Cancer
•Higher incidence male breast cancer

15. Disentangling SES and Inherent
Racial/Ethnic Cancer Risks
Clinical Trials Data
• Albain et al, JNCI 2009: Pooled analyses of
SWOG treatment trials for various cancers
– Equal treatments delivered through clinical trials
resulted in equal outcomes (regardless of race/ethnicity)
except for African Americans with hormonally-
driven cancers (breast & prostate cancers)
Recurrence Mortality
Premenopausal 1.39
(1.12-1.73)
1.41
(1.10-1.82)
Postmenopausal 1.45
(1.27-1.66)
1.49
(1.28-1.73)

16. TIME.com Aug 22, 2009
“Why Racial Profiling Persists in
Medical Research”

17. 0
20
40
60
80
100
120
140
160
1973
1975
1977
1979
1981
1983
1985
1987
1989
1991
1993
1995
1997
1999
2001
2003
2005
2007
African American Incidence
White American Incidence
African American Mortality
White American Mortality
SEER Program: Breast Cancer Incidence and
Mortality Rates, 1973-2007
Surveillance, Epidemiology and End Results Program; Cancer.gov

18. 0
20
40
60
80
100
120
140
160
1973
1975
1977
1979
1981
1983
1985
1987
1989
1991
1993
1995
1997
1999
2001
2003
2005
2007
African American Incidence
White American Incidence
African American Mortality
White American Mortality
SEER Program: Breast Cancer Incidence and
Mortality Rates, 1973-2007
Tamoxifen
Surveillance, Epidemiology and End Results Program; Cancer.gov
“Parsing the
Etiology of Breast
Cancer Disparities”
Newman, JCO
2016

19. Disparities in Breast Tumor Biology:
ER-Negative Breast Cancer in the U.S.
22%
39%
25%
31%32%
0%
5%
10%
15%
20%
25%
30%
35%
40%
45%
White American African
American
American Indian Asian/Pacific
Islander
Hispanic/Latina
American
ProportionER-NegativeBreastCancer
Li et al; SEER Data, 1992-98
Arch Int Med 2003

20. H&E ER-Neg PR-Neg HER2/neu-Neg
ER-Pos PR-Pos HER2/neu-PosH&E
Clinical Relevance of
Triple Negative Breast Cancer (TNBC)
• Inherently more aggressive pattern of breast cancer
Approximately 80% intrinsic basal subtype
• Fewer systemic therapy options for TNBC;
no targeted therapies
• More common in families with hereditary cancer
susceptibility, such as BRCA1 mutation carriers

21. Dataset/Sample Size
Frequency of TNBC
AA WA P
Carey, 2006 97 premenopausal AA vs 164
premenopausal WA women; Carolina
Breast Cancer Study
39% 16% <0.001
Morris, 2007 2230 Thomas Jefferson Univ Hosp pts;
197,274 SEER pts 20.8% 10.4% <0.0001
Lund, 2008 Population-based Atlanta GA cohort of 116
AA, 360 WA pts
46.6% 21.8% <0.001
Lund, 2008 167 AA and 23 WA from Grady Hospital;
Atlanta, GA
29.3% 13.0% 0.05
Moran, 2008 99 AA; 968 WA BCS pts from Yale Univ
School of Medicine
21% 8% <0.0001
Chavez-MacGregor,
2013
606 cases of male breast cancer,
population-based California Cancer
Registry
9% 3% NR
Frequency of “Triple Negative Breast Cancer” (TNBC)

22. “Breast cancer statistics, 2015:
Convergence of incidence rates between
black and white women”
CA: A Cancer Journal for Clinicians
29 OCT 2015
Δ=42%

23. Kohler B et al, April 2015
TNBC WA
TNBC AA
TNBC Asian/PI TNBC Hispanic
“Annual report to the nation on the status of cancer,
1975-2011, featuring incidence of breast cancer
subtypes by race/ethnicity, poverty, and state”

24. Population-Based Incidence Rates of TNBC,
by Race/Ethnicity and Age:
Implications for Screening Recommendations
Delayed mammography screening may worsen breast
CA outcome disparities between AA and WA women
(Amrikia and Newman, CANCER, 2011)
0
10
20
30
40
50
60
70
< 40 40-49 50-59 60-74 ≥75
IncidenceRate(per
100,000)
Age (years)
White
Black

25. Current Screening Mammography Guidelines:
Agreement regarding ACCESS to mammography beginning at 40
American Academy of Family
Physicians
 Women ages 50-74 years should undergo biennial screening mammography
 Women aged 40-49 should make an individualized decision regarding
screening mammography after considering risks and benefits
American Cancer Society
 Initiate annual screening mammography at age 45 years
 Transition to biennial screening mammography at age 55
 Annual screening mammography should be available to women at age 40
years; continuing until life expectancy is at least ten years.
American Coll OB-GYN  Annual mammography should be offered beginning at age 40 years
American Coll Radiology;
Soc. of Breast Imaging
 Women should have annual mammography beginning at age 40 years
American Soc. of Breast Surgeons
 Annual mammographic screening for women ages 45-54
 Shared decision-making for mammography in women ages 40-44
 Shared decision-making regarding annual versus biennial mammographic screening for women aged 55 and older
 Biennial mammography screening for women over age 75 with life expectancy at least ten years
NCCN  Women should have annual mammography beginning at age 40 years
US Preventive Services Task Force
 Women ages 50-74 should undergo biennial screening mammography
 Women aged 40-49 should make an individualized decision regarding
screening mammography after considering risks and benefits
 Insufficient evidence available to make recommendations for women age 75 years and older

26. TNBC and Screening Mammography:
Early Detection Improves Outcomes!!!!
Memorial Sloan Kettering
• Ho et al, Cancer 2012
• 194 T1a/b N0 TNBC; 1999-2006
• 69% screen-detected
T1a/b N0
CTX
No
CTX
5-Yr Locoregional
Recurrence-Free Survival
96.2% 96%
5-Yr Distant Mets-Free
Survival
95.9% 94.5%
National Comprehensive Cancer Network
• Vaz-Luis et al, JCO 2014
• 363 T1a/b N0 TNBC; 2000-09
• 75% screen-detected
T1a N0 T1b N0
CTX
No
CTX
CTX
No
CTX
5-Yr Overall
Survival
100% 94% 96% 91%
5-Yr Distant Mets-
Free Survival
100% 93% 96% 90%

27. Triple Negative Breast Cancer and African
Ancestry: England, Switzerland and Brazil
• Bowen et al, British J of Cancer 2008: London
• 22% among Blacks vs 15% among Whites (overall)
• 25% among Blacks vs 12% among Whites (<60yrs)
• Copson et al, British J of Cancer 2014: UK POSH Study
• 26% among Blacks vs 18% among Whites, all ≤40 yo
• Carvalho et al, BMC Women’s Health 2014: Brazil
• Highest TNBC frequency in regions with increased African ancestry
• Rapiti et al, Cancer Medicine 2016:
Switzerland
Swiss 1 (ref)
European 1.22
African 2.52
North American 2.18
Central/South American 2.15

28. High-Risk Breast Cancer and
African Ancestry
• Parallels between hereditary
breast cancer and breast cancer in
women with African ancestry
– younger age distribution
– increased prevalence of ER-negative,
high-grade tumors and TNBC
– higher risk of male breast cancer
• Is African ancestry associated
with a heritable marker for high-
risk breast cancer subtypes?
•Unique opportunity to gain insights regarding etiology
of breast cancer disparities and the pathogenesis of
triple-negative breast cancer

29. International Breast Cancer Research
Collaborative
Overarching Goal: To evaluate association between
African ancestry & high-risk breast cancer subtypes
• Step 1: Characterize the breast cancer burden
of Sub-Saharan Western Africa
– Komfo Anoyke Teaching Hospital, Kumasi Ghana

30. Michigan-Ghana Breast Cancer Research
Collaborative
Overarching Goal: To evaluate association between African
ancestry & high-risk breast cancer subtypes
• Step 2: Compare WA, AA, and Ghanaian pts
– Henry Ford Hospital, Detroit; KATH, Ghana
WA
N=321
AA
N=272
Ghana
N=234
PValue
Average
Age
63 60 48.0 0.002
TNBC 16% 26% 53% <0.001
Jiagge & Newman, J Global Onc 2016 “Ten-Year Anniversary Review”

31. Korle Bu Teaching Hospital 2010
Accra, Ghana
58%26%
5%
4%
2% 2%
2%
1%
Molecular Marker Pattern
ER neg/PR neg/HER2 neg
(TNBC)
ER neg/PR neg/HER2 pos
ER pos/PR neg/HER2 neg
ER neg/PR pos/HER2 neg
ER neg/PR pos/HER2 pos
ER pos/PR pos/HER2 neg
ER pos/PR pos/HER2 pos
ER pos/PR neg/HER2 pos
TNBC
Der and Newman, The Breast J, 2015
N=219

32. Breast Cancer Phenotypes in WA, AA,
Ghanaians and Ethiopians
Jiagge, Newman Ann Surg Onc 2016
80.20%
15.50%
62.90%
29.80%
32.50%
53.20%
71.30%
15.00%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
ER-positive TNBC
White American African American Ghanaian Ethiopian
P<0.0001
P<0.0001

33. GHANA
ETHIOPIA
Biologic Plausibility: “Oncologic Anthropology”
African Diaspora/ Patterns of Forced Population Migration

34. Breast Cancer Phenotypes and
East/West African Ancestry in USA
• Jemal A and Fedewa S,
– Breast Cancer Res Treat, 2012
• SEER Registry, 1996-2008
• Frequency of ER-negative breast cancer
–183,777 White American patients: 21%
–24,639 African American patients: 39%
–143 West African-born patients: 40%
–186 East African-born patients: 22%

35. Biologic Plausibility: “Oncologic Anthropology”
Malaria; Selection pressure for Duffy-null; African Diaspora
Duffy-Null Frequency
African Americans: 60-70%
White Americans: <5%
Duffy-Null Frequency
Ghanaians: 100%
Ethiopians: 50-60%

36. International Breast Cancer Research:
Eliminating the Threat of Breast Cancer Worldwide
International
Collaborations:
•Opportunities to study
variations in high-risk
patterns of disease
•Opportunities to
improve the standard of
health care in medically-
underserved populations
•Opportunities to cultural
and academic exchange
•Opportunities to forge
powerful friendships

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Mission: To reduce the global breast cancer burden through
advances in research and delivery of care to
diverse populations worldwide

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Thank You