Breast Cancer Treatment, Outcomes and Recent Advances

Ogori N Kalu, MD, MSDirector Breast Surgery-UHAsst. 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 Hispanic

Incidence

129.3 133.6

117.1 86. 91.8 122.2 123.5 118 84.7 91.1

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 SubtypesLuminal 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 ReceptorsER: estrogen receptorPR: progesterone receptorHER2: human epidermal growth factor receptor-2E2=estrogenEGF= epidermal growth factor

Target specific medications

Trastuzumab (Herceptin)AI=aromatase inhibitors (anastrozole, exemestane)TamoxifenLapatinib (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 Research2013

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 pregnancyImpact of infertility post treatment

Bone healthBone 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 cancerRadical Mastectomy : standard treatment

Retreat from Mastectomy

Lumpectomy + XRT

Optimizing local control

Minimizing disability

Minimizing disfigurement

Breast Cancer Treatment SURGERY

BREAST CONSERVATION MASTECTOMYLumpectomy, partial/segmental Simple/total

mastectomy or quadrantectomy Modified radical

mastectomy

Contraindicated in

RECONSTRUCTION hx of prior radiation Immediate v

delayedSize > 4cm; tumor:breast ratiopregnant 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 2007ALL Mastectomy Patients with CPM (Invasive -SEER)

Tuttle, T. M. et al. J Clin Oncol; 27:1362-1367 2009ALL Mastectomy Patients with CPM (DCIS-SEER)

Mastectomy and Breast ReconstructionTissue 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