1. Breast Cancer Treatment, Outcomes and Recent Advances
Ogori N Kalu, MD, MS
Director Breast Surgery-UH
Asst. Prof of Surgery
Rutgers NJ Med School

2. 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 Less than 1% of all new breast cancer cases occur in men
Among women aged years, breast cancer remains the leading cause of cancer death despite a steady decrease in breast cancer mortality since 1990.

3. Essex County Cancer Coalition*
Essex County Cancer Coalition

4. COMPARATIVE INCIDENCE & MORTALITY RATES,
NJ and US, FEMALES,
(NAACCR-age-adjusted rates per 100,000 (2000 US population standard))
Cancer Site
NJ 2006-
2010
US 2006-
BREAST
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
Mortality
25.2
25.1
30.9
11.7
13.2
22.6
22.1
30.8
11.5
14.8

5. 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%
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%
Unstaged
2.7%
2.5%
3.6%
2.8%
2.6%
API, Asian Pacific Islander; *Hispanic includes all races
Cancer Incidence and Mortality in New Jersey, , NJ DOH

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, , National Cancer Institute, Bethesda, MD.4
From Huo and Dignam in Kuerer’s Breast Surgical Oncology, 2010.

8. 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

9. 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: ; Cancer Causes and Control 2003, 14: )
Traditional socioeconomic, clinical, and pathologic factors do not account for the race-related stage difference at diagnosis for prostate cancer (JNCI 2001, 93: )
Breast cancer survival differs by race (AA versus EA) in an equal-access health care facility (Cancer 1998, 82: ; Cancer 2003, 98: )
Accounting for traditional risk factors explains differences in breast cancer incidence and outcome for all race/ethnic groups except African Americans (JNCI 2005, 97: )
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: )

10. 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)

11. 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

12. WHAT IS BREAST CANCER?

15. 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

16. HOW DO BREAST CANCER CELLS GROW?

17. Breast Cancer Receptors
ER: estrogen receptor
PR: progesterone receptor
HER2: human epidermal growth factor receptor-2
E2=estrogen
EGF= epidermal growth factor

18. Target specific medications
Trastuzumab (Herceptin)
AI=aromatase inhibitors (anastrozole, exemestane)
Tamoxifen
Lapatinib (Tykerb)

19. Early Breast Cancer Trialists' Collaborative Group (EBCTCG) :
Metaanalysis Tamoxifen Efficacy
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
The Lancet, Volume 378, Issue 9793, 2011,

20. Adjuvant Endocrine Therapy
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 ; p=0.004)
Increased arthralgia and bone fractures
Cuzick, et al, The Lancet Oncology, Volume 11, Issue 12, Pages , December 2010

22. 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

23. 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.

24. Pre-menopausal breast cancer
Unique Challenges Managing Breast Cancer in Young Women

25. Probability of Developing Breast Cancer Within the Next 10 years
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,

26. Estimated New Female Breast Cancer Cases and Deaths by Age, US, 2013
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
Modified from the American Cancer Society,
Surveillance and Health Service Research
2013

27. 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

28. 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: Cancer 2003:97:134-47)

29. Survival (%)
Age at Diagnosis (Years)
Five year relative survival of females diagnosed with breast cancer during , SEER 17

30. 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:

31. 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:
J Clin Oncol 2008;26:5561-8

32. 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

33. Breast Cancer Treatment
Advances in Surgical Management

34. 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

35. 1980 : 60 yr old woman with breast cancer Radical Mastectomy : standard treatment

36. Retreat from Mastectomy
Lumpectomy + XRT

38. Optimizing local control
Minimizing disability
Minimizing disfigurement

39. 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

40. Changing Patterns in Surgery
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
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

41. Contralateral Prophylactic Mastectomy Rates for Invasive and DCIS
Tuttle, T. M. et al. J Clin Oncol; 27:
ALL Mastectomy Patients with CPM (DCIS-SEER)
Tuttle, T. M. et al. J Clin Oncol; 25:
ALL Mastectomy Patients with CPM (Invasive -SEER)

42. Mastectomy and Breast Reconstruction
Tissue expander placement, followed by permanent implant

43. Skin sparing mastectomy

47. 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