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Breast Cancer Treatment, Outcomes and Recent Advances

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.

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Breast Cancer Treatment, Outcomes and Recent Advances

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  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 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.

  3. * Essex County Cancer Coalition

  4. COMPARATIVE INCIDENCE & MORTALITY RATES, NJ and US, FEMALES, 2006-2010 (NAACCR-age-adjusted rates per 100,000 (2000 US population standard))

  5. Distribution of Stage at Diagnosis of Breast Cancer, Females, 2006-2010 API, Asian Pacific Islander; *Hispanic includes all races Cancer Incidence and Mortality in New Jersey, 2006-2010, 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, 1975-2005, National Cancer Institute, Bethesda, MD.4 From Huo and Dignam in Kuerer’s Breast Surgical Oncology, 2010.

  7. 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

  8. 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)

  9. 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)

  10. 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

  11. WHAT IS BREAST CANCER?

  12. 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

  13. HOW DO BREAST CANCER CELLS GROW?

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

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

  16. 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, 771 - 784

  17. 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 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

  18. 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

  19. 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.

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

  21. Probability of Developing Breast Cancer Within the Next 10 years American Cancer Society Breast Cancer Facts & Figures, 2011-2012.

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

  23. 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

  24. 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)

  25. Survival (%) Age at Diagnosis (Years) Five year relative survival of females diagnosed with breast cancer during 2000-2005, SEER 17

  26. 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

  27. 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

  28. 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

  29. Breast Cancer Treatment Advances in Surgical Management

  30. 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

  31. 1980 : 60 yr old woman with breast cancerRadical Mastectomy : standard treatment

  32. Retreat from Mastectomy Lumpectomy + XRT

  33. Optimizing local control • Minimizing disability • Minimizing disfigurement

  34. 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

  35. 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

  36. Contralateral Prophylactic Mastectomy Rates for Invasive and DCIS Tuttle, T. M. et al. J Clin Oncol; 27:1362-1367 2009 ALL Mastectomy Patients with CPM (DCIS-SEER) Tuttle, T. M. et al. J Clin Oncol; 25:5203-5209 2007 ALL Mastectomy Patients with CPM (Invasive -SEER)

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

  38. Skin sparing mastectomy

  39. 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

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