African Americans and High-Risk/Triple Negative Breast Cancer:

Implications for Screening Mammography Recommendations

Lisa A. Newman, MD, MPH, FACS, FASCO Henry Ford Health System

Director, Breast Oncology Program Director, International Center for the Study of Breast Cancer Subtypes

Adjunct Professor of Surgery, M.D. Anderson Cancer Center

Primary Health Care of Women 25th Annual Conference

I have no disclosures

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

Breast Cancer Burden of African Americans

•  Socioeconomic Disparities

•  Tumor biology

•  Genetics

•  Lifestyle & Reproductive Experiences

•  Environmental exposures

•  Diet/Nutrition

•  Higher mortality

•  Advanced stage distribution

•  Younger age distribution

•  Increased risk of adverse tumor features

•  Higher incidence of male breast cancer

Utilization of Screening Mammography by Race/Ethnicity

•  Multiethnic Cohort (screening prevalence, 1999-2002) – White Americans 88.5% – African Americans 87.5%

•  Harmon et al, Cancer Epidemiol 2014

•  National Health Interview Survey 2015 (mammo within past 2 yrs) – White Americans 65% – African Americans 69%

•  ACS Breast Cancer Facts & Figures 2017-18

Disentangling Race and SES

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 Meta-analysis of breast cancer survival adjusted for SES

AA Mortality Hazard: 1.28 (95% CI 1.18-1.38)

Newman et al, JCO 2006

Pooled analysis of SWOG adjuvant therapy trials: Equal treatments resulted in equal outcomes for all cancers (regardless of race/ethnicity) except for African Americans with hormonally-driven cancers (breast & prostate cancers) Albain et al, JNCI 2009

Recurrence Mortality Pre- menopausal

1.39 (1.12-1.73)

1.41 (1.10-1.82)

Post- menopausal

1.45 (1.27-1.66)

1.49 (1.28-1.73)

Breast Cancer Burden of African Americans

•  Socioeconomic Disparities

•  Delivery of Care •  Tumor biology •  Genetics •  Lifestyle &

Reproductive Experiences

•  Environmental exposures

•  Diet/Nutrition

•  Higher mortality

•  Advanced stage distribution

•  Younger age distribution 30-40% AA <50; 20% WA<50

•  Increased risk of adverse tumor features Two-fold higher rates TNBC in AA vs WA

•  Higher incidence male breast cancer

“Breast cancer statistics, 2015: Convergence of incidence rates between

black and white women”

CA: A Cancer Journal for Clinicians 29 OCT 2015

Δ=42%

Increased Prevalence of TNBC Among AA Patients Regardless of Age or Stage at Diagnosis

Breast Cancer Res Treat (2009) 113 : 357

TNBC more common in young women, and in AA women in all age categories

TNBC more common with more advanced stages, and in AA women at all stages of disease

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”

H&E ER-Neg PR-Neg HER2/neu-Neg

ER-Pos PR-Pos HER2/neu-Pos H&E

Clinical Relevance of Triple Negative Breast Cancer

•  Inherently more aggressive pattern of breast cancer

•  Fewer systemic therapy options for TNBC: no targeted therapies •  More common in African American women and in families with hereditary cancer susceptibility (BRCA 1) •  More likely to be mammographically-occult •  More likely to present as an interval cancer

Breast Cancer Survival Among African American Patients by Phenotype

SEER Program, AA pts Dx’d 2010-12 (n=19,836; 20% TNBC)

Akinyemiju et al, Br CA Res Tr 2015

African Ancestry as a Risk Factor for Early Onset Breast Cancer

•  Average age at breast cancer diagnosis – White/Caucasians: 61 years – African American: 57 years

•  Proportion of pts diagnosed <50 years: –  1/5 WA; 1/3 AA

•  Population-based incidence rates by age (per 100K) Age (yrs) White American African American 20-24 1.3 2.0 25-29 7.9 11.8 30-34 25.7 33.2 35-39 59.4 66.6 40-44 121.2 123.5

0.0

100.0

200.0

300.0

400.0

500.0

25-29 30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70-74 75-79 80-84 85+ Age

Incidence: White

Mortality: African American Mortality: White

Data sources: Incidence - North American Association of Central Cancer Registries, 2009. Mortality - National Center for Health Statistics, Centers for Disease Control and Prevention, 2009.

Rat

e pe

r 100

,000

Incidence: African American

US Female Breast Cancer Incidence & Mortality by Age and Race,

2002-2006

Meta analysis of invitation Screening RCT (USPSTF/Cancer Intervention and Surveillance Modelling Network)

Nelson H D et al. Ann Intern Med 2009;151:727-737 ©2009 by American College of Physicians

Updated Estimates: Screening Mammography Benefits Cancer Intervention and Surveillance Modeling Network

Screening Strategy

Total # mammograms

Total # Deaths Averted

Total # Negative Recalls

Total # Benign Biopsies

Annual, 40-84 y 90.2 million 29,369 6.8 million 481,260

Annual, 45-54 y; Biennial, 55-79 y 49 million 22,829 4.1 million 286,288

Biennial, 50-74 y 27.3 million 17,153 2.3 million 162,888

Arleo et al, Cancer, October 2017

Current Screening Mammography Guidelines: Agreement regarding ACCESS to mammography beginning at age 40 yrs

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 yearsAmerican 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

Are we seeing more young women with breast cancer???

1976 1979 1982 1985 1988 1991 1994 1997 2000 2003 20060

50

100

150

200

250

300

350

400

450Ra

te per

100,0

00

Year

Ages 50+

All ages

Ages 0-49

1976 1979 1982 1985 1988 1991 1994 1997 2000 2003 20060

50

100

150

200

250

300

350

400

450 B. In situ

Data source: Surveillance, Epidemiology, and End Results (SEER) Program, SEER 9 Registires, 1973-2006,Division of Cancer Control and Population Science, National Cancer Institute, 2009.

* Rates are age-adjusted to the 2000 US standard population within each age group.

Figure 4. Incidence Rates* of Invasive and In Situ Female Breast Cancer by Age, Adjusted for Delayed Reporting, US, 1975-2006

Year

All agesAges 0-49

Ages 50+

A. Invasive

Are We Seeing More Young Women with Breast Cancer?

Growth of US Female Population by Age Category US Census 1980-2010

0

5,000,000

10,000,000

15,000,000

20,000,000

25,000,000

Age 20-29 years Age 30-39 years Age 40-49 years

1980 1990 2000 2010 Rosenberg and Newman, JAMA Onc 2015

Brinton L A et al. JNCI J Natl Cancer Inst 2008;100:1643-1648

Are we seeing more young women with breast cancer: SEER Data

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

Incide

nceRa

te(p

er100,000)

Age(years)

White

Black

H&E ER-Neg PR-Neg HER2/neu-Neg

ER-Pos PR-Pos HER2/neu-Pos H&E

Clinical Relevance of Triple Negative Breast Cancer

•  Inherently more aggressive pattern of breast cancer

•  Fewer systemic therapy options for TNBC: no targeted therapies •  More common in African American women and in families with BRCA1 hereditary cancer susceptibility

•  More likely to be mammographically-occult •  More likely to present as an interval cancer

Outcomes by Tumor Subtype and Treatment for Sub-Centimeter, Node-Negative Breast Cancer:

Multi-Institutional NCCN Data 75% mammographically screen-detected No details on race-ethnic distribution

Ines Vaz-Luis et al. JCO 2014;32:2142-2150

©2014 by American Society of Clinical Oncology

NCCN Outcomes: Early-Detected TNBC (Vaz-Luis et al, JCO 2014)

T1aN0 T1bN0

No CTX With CTX No CTX With

CTX OS 94% 100% 91% 96%

BCSS 95% 100% 95% 98%

IDFS 86% 91% 81% 88%

DRFS 93% 100% 90% 96%

Early Stage TNBC: Detection and Outcomes

•  Memorial Sloan Kettering Cancer Center –  194 cases of T1b N0 TNBC, 1999-2006 –  69% detected by screening – Median follow-up 73 months –  58% received adjuvant CTX

Ho et al, Cancer 2012

CTX No CTX 5-Yr Locoregional-Free Survival 96.2% 96% 5-Yr Distant Recurrence-Free Survival 95.9% 94.5%

Favorable prognosis in patients with T1a/T1bN0 triple-negative breast cancers treated with multimodality therapy; Ho et al Cancer 2012; 69% screen-detected

Cancer Volume 118, Issue 20, pages 4944-4952, 5 MAR 2012 DOI: 10.1002/cncr.27480 http://onlinelibrary.wiley.com/doi/10.1002/cncr.27480/full#fig2

Early Stage TNBC: Detection and Outcomes

•  Brown Univ & Beth Israel Medical Center – 113 cases of T1b N0 TNBC, 1996-2010 – No details on screen detection rates – Median follow-up 64 months – 43% received adjuvant CTX – Five-Year Overall and Disease-Free Survival

rates >90% regardless of whether adjuvant CTX delivered Olszewski et al, Br CA Res Tr 2013

“Breast cancer precursors revisited: molecular features & progression pathways”

Reis-Filho J et al; Histopathology 2010

Henry Ford Health System Benign Breast Disease Cohort

•  Henry Ford Health System – Metropolitan Detroit – Approximately 30% African American patients

•  Benign Breast Disease Cohort –  female patients with benign breast biopsy –  1994-2005 – Age 40-70 years –  2,588 African Americans –  3,566 White Americans

Newman et al, JAMA Onc 2016

Subsequent Breast Cancers •  106 AA (4.1%) vs. 144 WA (4.0%); p= 0.363 •  Mean time to breast cancer diagnosis

– AA: 6.8 years vs. WA: 6.1 years (p= 0.188) •  Stage Distribution

– AA: 28% DCIS vs WA: 22% DCIS (p= 0.146) – No significant differences in stage distribution for

invasive cancers Subtype AA (%) WA (%) P-ValueER+ and/or PR+, HER2- 63.1% 71.3%

0.0300ER+ and/or PR+, HER2+ 7.7% 11.7%ER- /PR- and HER2+ 4.6% 9.6%ER-/PR- and HER2- (TNBC) 24.6% 7.4%

African Americans N=2,588

White/Caucasian Americans N=3,566

Henry Ford Health System Benign Breast Disease Cohort: TNBC Incidence

Newman et al JAMA ONC, Dec 2016

Summary

•  TNBC incidence higher in African American women at all ages

•  Outcomes better for TNBC when detected early, and CTX less likely to be necessary

•  Early detection of TNBC with screening mammography is feasible

•  Potential exists for disproportionately negative impact of delayed screening mammography in African American women

THANK YOU!!!!!!