Breast Cancer Treatment, Outcomes and

Recent Advances

Ogori N Kalu, MD, MS

Director Breast Surgery-UH

Asst. Prof of Surgery

Rutgers NJ Med School

National Statistics

1 in 8 women in the U.S. (12 - 13%) will develop invasive breast cancer over the course of her lifetime.

In 2010, an estimated 207,000 new cases of invasive breast

cancer were diagnosed in women in the U.S., along with 54,000 new cases of non-invasive (in situ) breast cancer; and an estimated 40,000 cancer related deaths were reported.

About 1,970 new cases of invasive breast cancer were

diagnosed in men in 2010. Less than 1% of all new breast cancer cases occur in men

Among women aged 20-59 years, breast cancer remains the

leading cause of cancer death despite a steady decrease in breast cancer mortality since 1990.

Essex

County

Cancer

Coalition

*

Cancer

Site

NJ

2006-

2010

US

2006-

2010

BREAST All

Races

White Black API Hispanic All

Races

White Black API Hispa

nic

Incidence 129.3 133.6 117.1 86. 91.8 122.2 123.5 118 84.7 91.1

Mortality 25.2 25.1 30.9 11.7 13.2 22.6 22.1 30.8 11.5 14.8

COMPARATIVE INCIDENCE & MORTALITY RATES,

NJ and US, FEMALES, 2006-2010

(NAACCR-age-adjusted rates per 100,000 (2000 US population standard))

Distribution of Stage at Diagnosis of Breast Cancer,

Females, 2006-2010

ALL RACES WHITE BLACK API HISPANIC*

BREAST

Total Cases 44,430 37,017 4,895 2,097 3,374

Percent 100% 100% 100% 100% 100%

In Situ 23.4% 23.5% 20.3% 27.9% 23.6%

Local 46.5% 47.7% 40.8% 41.3% 43.0%

Regional 22.6% 21.8% 28.8% 24.0% 26.4%

Distant 4.7% 4.5% 6.6% 4.1% 4.5%

Unstaged 2.7% 2.5% 3.6% 2.8% 2.6%

Trends in Female Breast Cancer Incidence and Death Rates by Race and Ethnicity, United States.

Rates are age-adjusted to the 2000 US Standard Population.

Data are from the SEER Cancer Statistics Review, 1975-2005, National Cancer Institute, Bethesda, MD.4

From Huo and Dignam in Kuerer’s Breast Surgical Oncology, 2010.

Does Cancer Health Disparity = Health Care

Disparity?

Income and education influence health insurance coverage and access to appropriate early detection, treatment and palliative care

Socioeconomic factors influence exposure to cancer risk factors: tobacco use, poor nutrition, physical activity, and obesity

Cultural factors influence health behavior, attitudes toward disease, and choice of treatment

Socioeconomic Factors and Access to Medical Care:

Are they the only Factors?

Socioeconomic factors account for stage differences at diagnosis for most cancers but not breast and prostate cancer (Cancer 2002, 94: 2844 - 2854; Cancer Causes and Control 2003, 14: 761 - 766)

Traditional socioeconomic, clinical, and pathologic factors do not account for the race-related stage difference at diagnosis for prostate cancer (JNCI 2001, 93: 388 - 395)

Breast cancer survival differs by race (AA versus EA) in an equal-access

health care facility (Cancer 1998, 82: 1310 - 1318; Cancer 2003, 98: 894 - 899)

Accounting for traditional risk factors explains differences in breast cancer incidence and outcome for all race/ethnic groups except African Americans (JNCI 2005, 97: 439 - 448)

Being insured and having access to medical care does not eliminate the survival disparity for African American women with breast cancer (JNCI Monogr 2005, 35: 88 - 95)

What about biology??

“While data suggest that access to

quality care is a factor in cancer

disparities, other factors also play a

major role, including tumor biology and

genetics”

(JNCI 2009, 101: 984

– 92)

Biology and Cancer Health Disparity

Race/ethnic disparity in prevalence of basal-like breast tumors (JAMA 2006, 295: 2492 – 2502)

Most common among young women of African descent

Caveat: Breast cancer survival disparity in US is irrespective of tumor ER status (JNCI 2009, 101: 993 – 1000)

High proportion of breast cancer patients in West Africa

present with high grade and triple negative disease (J Clin Oncol 2009, 27: 4514 – 21)

Race/ethnic differences in prevalence of 8q24 cancer

susceptibility markers (Nat Genet 2007, 39: 638 – 44 & 954 – 6; Genome Res 2007, 17: 1717 – 22)

Risk alleles are more common among African-Americans

WHAT IS BREAST

CANCER?

Genomic Subtypes

Luminal A: 40%; ER+ and/or PR+; HER2-, slow

growing, least aggressive, best prognosis

Luminal B: 10-20%; ER+ and/or PR+; HER2+ or high

proliferation rate

HER2-enriched: 10%; ER/PR-

Basal-like: 10-20%; ER/PR/Her2-; worst prognosis

Claudin-low: 10%; similar to basal-like

HOW DO

BREAST

CANCER

CELLS

GROW?

Breast Cancer

Receptors

ER: estrogen

receptor

PR: progesterone

receptor

HER2: human

epidermal growth

factor receptor-2 E2=estrogen

EGF= epidermal

growth factor

Target specific

medications

Trastuzumab

(Herceptin)

AI=aromatase

inhibitors

(anastrozole,

exemestane)

Tamoxifen

Lapatinib

(Tykerb)

Figure 5. Effects of about 5 years of tamoxifen on the 15-year probabilities of recurrence and of

breast cancer mortality, for ER-positive disease Outcome by allocated treatment in trials of about 5

years of adjuvant tamoxifen

Early Breast Cancer Trialists' Collaborative Group (EBCTCG) :

Metaanalysis Tamoxifen Efficacy

The Lancet, Volume 378, Issue 9793, 2011, 771 - 784

Effect of anastrozole and tamoxifen as adjuvant treatment for

early-stage breast cancer: 10-year analysis of the ATAC trial

The Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial

Compare efficacy and safety of anastrozole (1 mg) with tamoxifen (20 mg), as

adjuvant treatment for postmenopausal women with early-stage ER+ breast cancer.

Anastrazole compared with tamoxifen had improved :

• disease-free survival

• time to recurrence

• time to distant recurrence

• Fewer contralateral breast cancers as first event compared

to tamoxifen daily for 5 years (HR 0.60; 95% CI 0.42-085;

p=0.004)

• Increased arthralgia and bone fractures

Cuzick, et al, The Lancet Oncology, Volume 11, Issue 12, Pages 1135 - 1141, December 2010

Adjuvant Endocrine Therapy

Comparison of

overall survival

by disease

stage for

women with

triple negative

breast cancer

(TNBC) and

those with other

phenotypes

Adapted from Bauer et

al

Who gets triple negative

breast cancer? ANY WOMAN CAN GET TRIPLE NEGATIVE BREAST

CANCER

Highest representation in the following populations:

Women of African descent

Pre-menopausal women

BRCA gene mutation ( BRCA-1)

Younger age at menarche, higher parity, younger

age at full term pregnancy, shorter duration breast

feeding, and higher body mass index (BMI),

especially among pre-menopausal women.

PRE-MENOPAUSAL BREAST

CANCER

Unique Challenges Managing Breast

Cancer in Young Women

By age 20 1 out of 1,681

By age 30 1 out of 232

By age 40 1 out of 69

By age 50 1 out of 42

By age 60 1 out of 29

By age 70 1 out of 27

Lifetime 1 out of 8

American Cancer Society Breast

Cancer Facts & Figures, 2011-2012.

Probability of Developing Breast Cancer Within the Next 10 years

Age (yrs) In Situ

cases

Invasive

cases

Deaths

< 40 1900 10980 1020

<50 15,650 48,910 4,780

50-64 26,770 84,210 11,970

65+ 22,220 99,220 22,870

All ages 64,640 232,340 39,620

Estimated New Female Breast Cancer Cases and Deaths by Age, US, 2013

Modified from the American Cancer Society,

Surveillance and Health Service Research

2013

Different risk factors

compared to older women

More likely to be associated with an increased

familial risk (BRCA1, BRCA2, TP53, PTEN

mutations)

Obesity, high caloric intake, high alcohol use,

red meat, sedentary lifestyle

Recent OCP use, particularly for ER-negative

tumors

Early childbearing and multiparity

Variations according to race

and ethnicity

Women >45, breast cancer is more common in whites

than blacks

Black women under the age of 35 have 2X the incidence

of invasive breast cancer and 3X the mortality rate than

white women

Young black women with Stages II and IV disease had a

worse prognosis despite standard therapy

(Cancer Causes Control 2003;14:151-60. Cancer 2003:97:134-47)

Su

rviv

al

(%)

Age at Diagnosis (Years)

Five year relative survival of females diagnosed with breast cancer during 2000-

2005, SEER 17

Clinicopathologic Features

Cancers in women<40:

tumors were larger (P=.012)

of higher grade (P=.0001)

more lymph node positivity (P=.008)

lower ER positivity (P=.027)

higher rates of HER2/neu over-expression

(P=.075)

Inferior disease-free survival

(HR=1.32,P=.094)

J Clin Onc 2008;26:3324-30

Treatment: variations in

outcomes Women < 50 treated for breast cancer had

higher rates of second cancers (bone, ovary,

thyroid, kidney)

Women <36 y have 13% 10-year cumulative

incidence of contralateral breast cancer

Women <45 y: Both post lumpectomy and

mastectomy radiation conferred an additional

50% incr risk in contralateral breast ca

Cancer Epidem Biom Prev 2008;17:2647-55

J Clin Oncol 2008;26:5561-8

Considerations

Fertility and pregnancy

Impact of infertility post treatment

Bone health

Bone density loss after treatment; risk of long term

osteopenia, osteoporosis, fractures

Psychosocial issues

Adequate screening and risk assessment

Breast Cancer

Treatment

Advances in Surgical Management

History of Breast Cancer Surgery

1600 BC: Ancient Egyptians treated breast tumors with cauterization via “fire drill”

17/18th century: Jean Louis Petit, French surgeon linked the

concept that cancer spread via lymphatics. First to remove lymph nodes, breast, pectoral muscles

1882: William Stewart Halstead radical mx 1940s: modified radical mastectomy 1971: NSABP B-04: total mx= radical mx 1976: NSABP B-06: lump+ALND+rads=MRM 1999 (2004): NSABP B32: importance of SLNB 2010: ACOSOG Z0011: Futility of ALND for node postive

SLNB, for pts undergoing BCT and systemic therapy

1980 : 60 yr old woman with breast cancer

Radical Mastectomy : standard treatment

Retreat from Mastectomy

Lumpectomy + XRT

Optimizing local

control

Minimizing

disability

Minimizing

disfigurement

Breast Cancer Treatment

SURGERY BREAST CONSERVATION MASTECTOMY Lumpectomy, partial/segmental Simple/total mastectomy or quadrantectomy Modified radical mastectomy

Contraindicated in RECONSTRUCTION hx of prior radiation Immediate v delayed Size > 4cm; tumor:breast ratio pregnant women who would require radiation while pregnant

Changing Patterns in Surgery

Increasing mastectomy and CPM rates Freedom from imaging surveillance

▪ Imaging Fatigue or “No Mas” Syndrome Availability of better reconstructive

techniques Nipple-sparing mastectomies seemingly

oncologically safe

• removal of NAC is perceived as mutilating

• “…NAC seems to be the signature of the breast identity more than the volume or the shape….” J.Y. Petit 2009

Contralateral Prophylactic Mastectomy Rates

for Invasive and DCIS

Tuttle, T. M. et al. J Clin Oncol; 25:5203-5209 2007

ALL Mastectomy Patients with CPM (Invasive -SEER)

Tuttle, T. M. et al. J Clin Oncol; 27:1362-1367 2009

ALL Mastectomy Patients with CPM (DCIS-SEER)

Mastectomy and Breast

Reconstruction Tissue expander placement, followed by permanent implant

Skin sparing mastectomy

Final thoughts

Is breast cancer one disease or actually

multiple disease types each requiring a

unique treatment

Should different screening and treatment

algorithms be considered in younger

women

Will/should future treatment plans be

stratified by race