2017 Breast Cancer Update

Transcription

1 2017 Breast Cancer Update Alberto J Montero, M.D., MBA Quality Improvement Officer, Taussig Cancer Institute, Lerner College of Medicine Cleveland Clinic

2 N/A Disclosure

3 Overview Epidemiology (US/Global) Prevention screening guidelines Overdiagnosis Breast cancer, management

4 BREAST CANCER EPIDEMIOLOGY

5 U.S.

6 Global Incidence (per 100,000)

7 Global Incidence/Mortality

8 38% decrease breast cancer mortality

9 Breast Cancer U.S. Numbers Despite similar incidence ( k/yr) > 30% decrease in mortality (~35 k/yr) No screening or treatment Screening Treatment Both screening and treatment ½ from improved screening ½ from improved treatment An increasing proportion of breast cancer patients (by far the majority) are cured Year Berry DA et al, NEJM 2005

10 PREVENTION/SCREENING

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12 Recommendations For all asymptomatic patients, mammography screening guidelines begin as follows: History and physical to include complete medical history and clinical breast exam If physical exam negative, then risk assessment Average risk Increased risk prior hx of cancer, 5 yr risk > 1.7% (Gail), lifetime risk >20% based on models using family history, prior history of mantle radiation, women with strong pedigree or known genetic predisposition

13 Grading of Recommendations Recommendation evaluated by guideline panel members; strength of evidence identified using NCCN Categories of Evidence and Consensus Goal: Base recommendation on high-quality evidence from controlled clinical trials or meta-analyses; if little data available, lower-level evidence used (non-randomized trials; case series; clinical experience of expert physicians). Recommendation categories: Category 1: (high-level evidence) Uniform consensus intervention appropriate Category 2A: (lower level evidence) Uniform consensus intervention appropriate Category 2B: (lower level evidence) Consensus intervention appropriate Category 3: (any level evidence) Major disagreement intervention appropriate

14 Risk adapted approach Average lifetime breast cancer risk (12%) vs. high risk (>20%)

15 Gail Risk Model

16 Average Risk Patients No personal history of: breast, ovarian or pancreatic cancer prior breast biopsy showing LCIS, ADH, ALH radiation therapy to the chest wall at/before age 30 No family history of: breast cancer including men at any age, women diagnosed at or before age 50, two or more breast primaries in one relative at any age, or triple negative cancer ovarian cancer early onset pancreatic cancer (at or before age 50) No Ashkenazi Jewish ancestry No genetic predisposition (BRCA1 or BRCA2) in patient, or first, second, or third degree relative.

17 Average Risk High Risk lifetime breast cancer risk: 9% lifetime breast cancer risk: 73%

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19 Average Risk Patients Annual screening mammography beginning at age 40 Clinical breast exam (CBE): Every 1-3 years beginning at age 20 Annually starting at age 40 Diagnostic imaging as indicated For those who decline mammography or are not candidates, CBE should be performed as outlined above

20 Recommendations: Average risk, 40 and older Annual clinical encounter should include ongoing risk assessment, risk reduction counseling, clinical breast exam \No randomized trials comparing CBE vs no screening Recommended to maximize earliest detection of interval cancers Annual screening mammogram with consideration for tomosynthesis Combined digital mammography and DBT improve cancer detection, decrease callback rates; radiation dose doubled, but can be minimized using synthetic 2D reconstructions Breast awareness women should be aware of changes in their breasts and bring to attention of their providers

21 NCCN Recommendations Women should be counseled regarding benefits, risks, and limitations of screening No age cutoff if patient has limited life expectancy and she would not pursue intervention should abnormality be found, she should not undergo screening No recommendations for supplemental screening in women with dense breasts Endorsed insurance coverage for screening at all ages and intervals, not just USPSTF A and B

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23 USPSTF 2016 Conclusions

24 OVERDIAGNOSIS OF BREAST CANCER

25 Overdiagnosis- tumors detected on screening that never would have led to clinical symptoms (or adversely impacted survival)

26 Lead Time (information) Biassystematic error of apparent increased survival from detecting disease at an earlier (& subclinical) stage

27 Lead Time Bias and Overall Survival

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32 Cochrane Screening reduces breast cancer mortality by 15% Overdiagnosis and overtreatment = 30% Then, for every 2,000 women invited for screening over 10 years, 1 will avoid dying of breast cancer 10 healthy women, who would not have been diagnosed w/out screening will be treated unnecessarily. And, >200 women will experience important psychological distress because of FP findings.

33 BREAST CANCER BIOLOGY

34 Expression Subtype Basal-like HER2 (ER-negative) Immunohistochemical Surrogate ER/PR/HER2-negative CK5/6 or HER1+ HER2+ ER and PR-negative No (%) 100 (20%) 33 (7%) Luminal A ER or PR + HER2-negative Luminal B ER or PR + HER (51%) 77 (16%) Unclassified All markers negative 31 (6%) Total 496

35 Hierarchical clustering of primary breast tumors using the "intrinsic" subset of genes Lonning PE et al. (2005) Genomics in breast cancer-therapeutic implications. Nat Clin Pract Oncol 2:

36 Immune modulatory Mesenchymal Mesenchymal stem like Luminal Androgen Receptor

37 AJCC TNM Staging T tumor size T1 = < 2cm T2 = 2-5 T3 = >5 cm T4 = chest wall or skin involvement. N - ipsilateral lymph nodes N1 = 1-3 N2 = 4-9 N3 = 10+, infraclavicular, supraclavicular M distant metastases 0 : Tis I : T1N0 IIA:T0-1N1; T2N0 IIB:T2N1; T3N0 IIIA: T0-3 N2; T3N1 IIIB: any T4 IIIC: any N3 IV: M1

38 Breast cancers can look like this...or like this Low grade, more benign appearing High grade, aggressive appearing

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40 Prognostic relevance of LN

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42 Systemic Therapies for Breast Cancer

43 Hormone Receptor (ER/PR+)/HER2- breast 50% of breast cancers Increasing incidence w/age Less sensitive to chemotherapy 50% relapses >5 yrs cancer

44 EBCTCG: Lancet 2005; 365:

45 EBCTCG: Lancet 2005; 365:

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48 HER2+ breast cancer 25% of all breast cancers Prior to trastuzumab very poor prognosis aggressive clinical phenotype: highgrade tumors, more advanced stage, early systemic metastasis

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51 Triple Negative Breast Cancer ~20% cancers Poorest prognosis Younger age Present later Associated w/brca mutation Recurrence early <5 yrs

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53 EBCTCG: Lancet 2005; 365:

54 Conclusions Breast Cancer Outcomes have improved due to better screening & treatment Mammography screening as per NCCN or other consensus guidelines important Risk adapted approach, e.g. Gail Risk tool, may help mitigate problem of overdiagnosis Breast cancer treatment determined by biological subtype

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