What Every General Surgeon Should Know About Breast Cancer

Transcription

1 What Every General Surgeon Should Know About Breast Cancer Christina A. Finlayson, MD Associate Professor, Surgery Director, University of Colorado Hospital Breast Center

2 Outline How are we doing in the war against cancer? How do you order a mammogram? How do you stage breast cancer? What does medical oncology have to offer?

3 Change in the US Death Rates by Cause, 1950 & Rate Per 100, Heart Diseases Cerebrovascular Diseases Pneumonia/ Influenza Cancer

4 Five-year Relative Survival (%) during Three Time Periods By Cancer Site Site All sites Breast (female) Colon Lung and bronchus Melanoma Pancreas Prostate

5 Cancer Survival UCCC vs. Colorado 2006

6 Breast Cancer ,920 women diagnosed with invasive breast cancer 40,970 women will die from breast cancer 2 million women living who have been treated for breast cancer Risk of developing invasive breast cancer is 1 in 8 Risk of dying from breast cancer is 1 in 33 American Cancer Society, 2006

7 What Every Surgeon Should Know About Breast Cancer Radiology

8 Screening Guidelines for the Early Detection of Breast Cancer, American Cancer Society 2003 Patient is asymptomatic Insurance doesn t require a referral Doesn t require a physician order Mammographer is not on site

9 Screening Guidelines for the Early Detection of Breast Cancer, American Cancer Society 2003 Yearly screening mammograms are recommended starting at age 40 for women of average risk and continuing for as long as a woman is in good health

10 Mammogram Prevalence , USA All women 40 and older Prevalence (%) Women with less than a high school education Women with no health insurance Year

11 How Good is Mammography? 8 Randomized Controlled Trials 1960s % reduction in breast cancer mortality Sensitivity Mammography: 85% Physical Exam: 50% But, with the advances in equipment, film, and training, the sensitivity of mammography has

12 gone down. The actual sensitivity of screening mammography in clinical practice today is about 70% False negative mammogram: biopsy proven cancer within a year of a negative screening mammogram

13 Why is mammography doing worse? Prevalence cancers slow growing, large cancers in the population waiting to be found Incidence cancers develop more than one year after initial screen Interval cancers become clinically evident less than one year from last screen

14 Why is mammography doing worse? The sensitivity of mammography is determined by competing methods of diagnosis Women are more sensitive to detecting lumps and much more likely to bring them to medical attention Providers are also more aware

15 If mammography misses so much, is it worth screening? About 10 years after mammographic screening became widespread in the U.S., mortality from breast cancer started to drop.

16 USA mortality: USA - Age-adjusted Breast Cancer Mortality

17 If mammography misses so much, is it worth screening? We cannot be sure that the change is due to screening, but there is a good correlation:

18 Sweden has a tremendous yearly screening program: Sweden - Age-adjusted Breast Cancer Mortality

19 Great Britain also screens, but only every 3 years: U.K. - Age-adjusted Breast Cancer Mortality

20 while Denmark has no screening program: Denmark - Age-adjusted Breast Cancer Mortality

21 Is there a better screening test? No! Mammography is the best single screening test for women of average risk. Mammo + Physical Examination is a potent combination for screening

22 Screening Guidelines for the Early Detection of Breast Cancer, ACS 2003 Women at increased risk should talk with their doctors about the benefits and limitations of starting mammography screening earlier, having additional tests (i.e., breast ultrasound and MRI), or having more frequent exams.

23 Who are women at increased risk? Family history first degree relative Extended family history Previous biopsy Atypical hyperplasia LCIS BRCA1/BRCA2 (Radiation to chest wall)

24 Imaging options Mammography Ultrasound MRI, contrast enhanced

25 Mammography Gold-standard Multiple studies with mortality as end-point Decreases mortality from breast cancer by at least 25-50% Detection rate: 5-7/1000 for first mammogram 2-3/1000 for subsequent mammograms

26 Screening Ultrasound Ultrasound plus mammography finds more cancers than mammography alone Cancers seen by ultrasound are usually invasive Many false positives -- many extra biopsies U/S adds 1-2 cancer / 1000 screens Not covered by insurance for screening

27 Screening MRI Warner, E. JAMA, 2004

28 Screening BRCA1/2: 22 Cancers Detected Mammogram Ultrasound MRI Screened Sensitivity 38% 25% 85% Specificity 99.6% 95% 93% PPV 83% 23% 42% NPV 97% 96% 99% Warner, E. JAMA, 2004

29 ACS Guidelines for Breast Screening with MRI Recommend Annual MRI Screening (Based on Evidence) BRCA mutation First-degree relative of BRCA carrier, but untested Lifetime risk ~20 25% or greater, as defined by BRCAPRO or other models that are largely dependent on family history CA Cancer J Clin 2007

30 ACS Guidelines for Breast Screening with MRI Recommend Annual MRI Screening (Based on Expert Consensus Opinion) Radiation to chest between age 10 and 30 years Li-Fraumeni syndrome and first-degree relatives Cowden and Bannayan-Riley-Ruvalcaba syndromes and first-degree relatives CA Cancer J Clin 2007

31 ACS Guidelines for Breast Screening with MRI Insufficient Evidence to Recommend for or against MRI Screening Lifetime risk 15 20%, as defined by BRCAPRO or other models that are largely dependent on family history Lobular carcinoma in situ (LCIS) or atypical lobular hyperplasia (ALH) Atypical ductal hyperplasia (ADH) Heterogeneously or extremely dense breast on mammography Women with a personal history of breast cancer, including ductal carcinoma in situ (DCIS) CA Cancer J Clin 2007

32 ACS Guidelines for Breast Screening with MRI Recommend Against MRI Screening (Based on Expert Consensus Opinion ) Women at <15% lifetime risk CA Cancer J Clin 2007

33 High Risk Screening: Cost Clinical Breast Exam $ Mammogram Bilateral MRI

34 Diagnostic Imaging

35 Diagnostic Imaging Workup of an abnormal screening mammogram Evaluation of a palpable abnormality or other breast complaint Evaluates characteristics of palpable mass Screens remainder of breast Imaging of breast cancer after diagnosis No emergency mammograms Radiologist available to interpret at time of imaging

36 Diagnostic Imaging Workup of an abnormal screening mammogram

37 BIRADS Assessments 0 Additional imaging evaluation needed 1 - Negative (routine screening) 2 - Benign (routine screening) 3 - Probably (6m f/u) 4- Suspicious (biopsy) 5 - Highly suspicious (biopsy) 6 Known, biopsy proven cancer (**New!!**)

38 CC MLO

39 Spot compression Magnification

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42 Spot compression Magnification

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44 Ultrasound evaluates a mammographic mass

45 Diagnostic Imaging Evaluation of a palpable abnormality or other breast complaint Evaluates characteristics of palpable mass Screens remainder of breast

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47 Ultrasound of palpable mass

48 Diagnostic Imaging Imaging of breast cancer after diagnosis No emergency mammograms

49 Imaging after diagnosis

50 MRI Ipsilateral Breast Multifocal/Multicentric Pre-Contrast Post-Contrast

51 MRI Contralateral Breast MRI Evaluation of the Contralateral Breast in Women with Recently Diagnosed Breast Cancer Lehman CD, et al NEJM Mar 29, 2007

52 MRI Contralateral Breast 25 institutions Minimum 50 MRIs Minimum 5 MRI biopsies 969 participants 30 cancers detected (3.1%) 10% false positive biopsies NPV 99%

53 MRI Contralateral Breast The current cost of MRI precludes its widespread use in general populations, but this imaging tool appears to improve the detection of cancer in women at increased risk, such as women with a recent diagnosis of breast cancer. Lehman et al, 2007

54 What Every Surgeon Should Know About Breast Cancer Lymph Node Staging

55 Predictors of Breast Cancer Survival Tumor size Lymph node metastasis

56 Predictors of Breast Cancer Tis noninvasive T1 < 2 cm Survival - Tumor size T2 greater than 2 cm but not greater than 5 cm T3 greater than 5 cm T4 chest wall, skin or inflammatory involvement

57 Predictors of Breast Cancer Survival Clinical staging Lymph node metastases cn0 no regional lymph node metastases cn1 positive lymph nodes, movable cn2 matted lymph nodes or positive internal mammary nodes cn3 positive infraclavicular nodes or internal mammary + axillary nodes or supraclavicular nodes

58 Predictors of Breast Cancer Survival Lymph node metastases Pathologic staging pn0 no regional lymph node metastases Single tumor cells or clusters < 0.2 mm pn0(i-) IHC negative pn0(i+) IHC positive pn0(mol-) RT-PCR negative pn0(mol+) RT-PCR positive

59 Predictors of Breast Cancer Survival Lymph node metastases pn1 positive regional nodes pn1a 1-3 positive axillary LN pn1b positive internal mammary nodes found by SNBx only pn1c = pn1a+pn1c

60 Predictors of Breast Cancer Survival Lymph node metastases pn2 positive regional nodes pn2a 4-9 positive axillary LN (at least one >2 mm) pn2b positive internal mammary nodes clinically apparent

61 Predictors of Breast Cancer Survival Lymph node metastases pn3 positive regional nodes pn3a >10 positive axillary LN (at least one >2 mm) or infraclavicular LN positive pn3b positive internal mammary nodes clinically apparent + pos axillary nodes pn3c positive supraclavicular nodes

62 Predictors of Lymph Node Metastasis Tumor size Lymphovascular invasion Tumor grade Patient age

63 Axillary Node Dissection

64 Axillary Node Dissection Lymphedema Parasthesias Pain Shoulder dysfunction

65 Definitions Axillary lymph node dissection

66 DefinitionsLymphatic Mapping

67 Definitions- Sentinel lymph node Lymph nodes identified by lymphatic mapping Clinically suspicious lymph nodes

68 Definitions- Sentinel lymph node biopsy

69 Consensus statements American Society of Breast Surgeons Institute for Clinical Systemic Improvement Canadian Steering Committee Consensus Conference Committee, Philadelphia German Society of Senology

70 Philadelphia Consensus Conference Sentinel node biopsy can replace routine axillary lymph node dissection for patients with no disease in the sentinel lymph node, with no further axillary treatment necessary. Schwartz GF, Giuliano AE, Veronesi U, et al Cancer, 2002

71 Specific situations Positive sentinel node biopsy Large tumors Inflammatory breast cancer Multicentric tumors DCIS Male breast cancer Pregnancy Internal mammary nodes Prior breast or axillary surgery

72 Positive sentinel lymph nodes 48% of patients with a positive sentinel lymph node will have additional disease found at axillary node dissection

73 Positive sentinel lymph nodes Immunohistochemistry upstages H&E negative lymph node status in 10% of patient pn0i+ Node deposits <0.2 mm are also pn0 No recommendation on axillary node dissection

74 Positive sentinel lymph nodes Micrometastases Node deposits 0.2<2.0 mm 20-35% will have additional positive LNs

75 Are there alternatives? Predictive models Axillary Radiation

76 Predictive models: Van Zee: Ann Surg Oncol, 2003

77 Axillary Radiation NSABP B-04 (1985) 818 patients clinically node negative MRM, TM+XRT, or TM alone 10 year axillary recurrence 1.4% (MRM) vs 3.1% (TM+XRT)

78 Axillary Dissection vs Radiation Where is the sentinel lymph node?

79 Surgeons view of the axilla

80 Radiation Oncologists view of the axilla

81 What we did: T4 2: Interest point viewed on AP DRR; vertebral body level and distance to inferior border of clavicle evaluated

82 What we did: 3: Interest point evaluated relative to previously designed tangential whole breast fields

83 Relationship of SLN to Tangent A: inside treated field - 78% B: under corner block - 12% C: outside of field - 10% A+B: if removed corner block - 90% A=78% C=10% B=12% Rabinovitch et al Center University of Colorado Cancer

84 SLN Position and Tangent Fields Key Findings/Conclusions Position of SLN relative to vertebral body level Ranges from T2-T7 most often opposite T4 on an AP view Relationship of SLN to tangents Outside of field 10% Under supero-posterior block 12% Within treated field 78% Relationship of SLN to clavicle Located inferior to clavicle in 94% 90% within treated field if remove corner block Most superior SLN was located 1.5 cm above base of clavicle Conclusions: Extension of tangents to 1.5 cm above bottom of clavicle would include SLN in 100% of patients Nearly all SLNs (94%) are located outside of traditional axillary radiotherapy fields If corner block removed, SLN within treated tangents 90%

85 Ongoing studies NSABP B-32 Randomized SN- patients to ALND vs. no further surgery EORTC Randomized SN+ patients to ALND vs. axillary radiation ACOSOG Z0011 Randomized SN+ patients to ALND vs. no further therapy (tangential breast radiation only)

86 Panel recommendations No ALND No recommendation ALND Negative SN IHC+ SN Micrometastases 0.2mm<2 mm Deposits <0.2 mm Macrometastases >2mm

87 Multicentric Tumors 10% of presenting breast cancers Tumor in more than one quadrant or separated by more than 2 cm Peritumoral vs. Subareolar injections SNBx performance similar to patients with unifocal disease

88 Ductal Carcinoma in Situ 5-15% are IHC positive SNBx if local treatment is mastectomy

89 Male Breast Cancer 1700 male breast cancers diagnosed annually Survival equivalent for women with similar stage Treatment of male breast cancer parallels treatment for women Unlikely the SNBx would be less accurate

90 Pregnancy Vital dye (lymphazurin) contraindicated Radiolabled colloids probably safe Insufficient data for specific recommendations

91 Internal mammary lymph nodes No survival advantage Rarely site of local recurrence Likelihood of SN site 10% Likelihood of metastatic involvement 1% Insufficient data for specific recommendations

92 Prior breast surgery Prior diagnostic or excisional breast biopsy not a contraindication Breast reduction may be contraindication for tumors in the lower or medial aspect of the breast Breast augmentation with submammary or subpectoral implants probably not a contraindication Minimal data

93 Conclusions Sentinel lymph node biopsy replaces axillary dissection in most situations An axillary dissection should be performed for most patients with positive sentinel nodes Morbidity from breast cancer treatment is decreased by limiting axillary dissection to patients with positive lymph nodes.

94 What Every Surgeon Should Know About Breast Cancer Medical Oncology

95 Medical Oncology Neoadjuvant chemotherapy Genetic profiling - Oncotype

96 Medical Oncology Neoadjuvant chemotherapy

97 Inflammatory breast cancer: T4d N3c M1

98 Rational of Neoadjuvant Chemotherapy What we learned from inflammatory breast cancer Local vs. systemic disease

99 Effect of Preoperative Chemotherapy on Local-Regional Disease in Women With Operable Breast Cancer: Findings From National Surgical Adjuvant Breast and Bowel Project B-18 Bernard Fisher, et al J Clin Oncol 1998

100 Effect of Preoperative Chemotherapy Disease Free Survival no effect Distant DFS no effect Overall Survival no effect Breast conservation 20% increase

101 Pre-NeoAdjuvant Chemotherapy Pre-contrast Post-contrast

102 Post-NeoAdjuvant Chemotherapy Pre-contrast Post-contrast

103 Neoadjuvant Chemotherapy Who should get it? Inflammatory breast cancer T3/4 tumors not amenable to immediate surgery Large tumor volume to breast volume ratio desiring breast conservation Clinically palpable lymph nodes

104 Neoadjuvant Chemotherapy What should they get? Chemotherapy Adriamycin? Herceptin? Antiendocrine therapy Aromatase Inhibitor

105 Medical Oncology Genetic profiling Oncotype

106 Medical Oncology 55 year old woman treated with lumpectomy/sentinel node biopsy 3 cm High grade ER 60% PR 10% Her-2-neu negative

107 Oncotype Dx Produced by Genomic Health RNA from tumor extracted and purified RT-PCR of 21 genes Reverse transcription polymerase chain reaction Recurrence score calculated Based on proprietary Oncotype algorithm of gene expression

108 Oncotype Dx 21 Gene Assay

109 21 Gene Panel Analyzed by RT-PCR

110 What is sent in? 10 micron section of breast tumor from formalin fixed paraffin embedded tissue submitted x 6 1 H&E slide from same block

111 $3460

112 A Multigene Assay to Predict Recurrence of Tamoxifen-Treated, Node-Negative Breast Cancer Soonmyung Paik, M.D., Steven Shak, M.D., Gong Tang, Ph.D., Chungyeul Kim, M.D., Joffre Baker, Ph.D., Maureen Cronin, Ph.D., Frederick L. Baehner, M.D., Michael G. Walker, Ph.D., Drew Watson, Ph.D., Taesung Park, Ph.D., William Hiller, H.T., Edwin R. Fisher, M.D., D. Lawrence Wickerham, M.D., John Bryant, Ph.D., and Norman Wolmark, M.D. Volume 351: December 30, 2004 Number 27

113 Tumors from patients enrolled on 2 NSABP trials analyzed: NSABP B-14 ER+ LN- breast cancer Tamoxifen (n= 290) vs. Placebo (n=355) NSABP B-20 ER+ LN- breast cancer Tam (n=227) vs. Tam/CMF (n=434)

114 Recurrence Score Low Risk Intermed Risk High Risk Oncotype Score >31 10-yr distant recurrence rate 7% 14% 30%

115 Treatment benefit T amoxi f e n bene f i t by r ec ur r ence sc or e Pl acebo T amoxi f en R e c u r r e n c e s c o r e

116 Treatment benefit CMF benefit by recurrence score Survival Tamoxifen CMF Recurrence score

117 When to order Oncotype Dx Newly diagnosed breast cancer Stage I/II, node negative T1N0 or T2N0 ER+ To be treated with Tamoxifen No data on aromatase inhibitors, ER-, or node + patients

118 Rate of Distant Recurrence as a Continuous Function of the Recurrence Score

119 Implications for Therapy Recurrence score of <18 (Low Risk) No benefit from chemotherapy Benefit from tamoxifen Recurrence score of > 31(Hi risk) Large absolute benefit from chemotherapy Absolute increase in DRFS at 10 yrs 27.6%

120 Medical Oncology 55 year old woman treated with lumpectomy/sentinel node biopsy 3 cm High grade ER 60% PR 10% Her-2-neu negative

121 Oncotype Score 37

122 Oncotype Score 37 Average 10 year Risk of Distant Recurrence Tamoxifen only - 25% Tamoxifen + CMF - 9% Absolute benefit 16% Relative benefit 66%

123 Conclusion Breast cancer is not one disease Biologic markers are being identified that predict response to treatment Therapy is being tailored to specific tumor characteristics, increasing benefit and decreasing risk