Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic...

52
Benign Benign Breast Breast Disease – Disease – Focus on Focus on Atypia Atypia Lynn C. Hartmann, MD Lynn C. Hartmann, MD Women’s Cancer Program Women’s Cancer Program Mayo Clinic Cancer Center Mayo Clinic Cancer Center

TAGS:

Transcript of Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic...

Page 1: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Benign Breast Benign Breast Disease –Disease –Focus on Focus on

AtypiaAtypia

Lynn C. Hartmann, MDLynn C. Hartmann, MD

Women’s Cancer ProgramWomen’s Cancer Program

Mayo Clinic Cancer CenterMayo Clinic Cancer Center

Page 2: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

• 1967-2001: 13,647 women 1,173 cancers

• Iowa SEER Registry for comparison

• Mayo Benign Breast Disease Cohort

Page 3: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Breast Carcinogenesis Breast Carcinogenesis (presumed)(presumed)

Benign Breast Disease Breast Cancer

Page 4: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

BBD: Risk PredictionBBD: Risk Prediction

Relative risks by histologyRelative risks by histology

Non-Non-proliferativeproliferative

ProliferativeProliferativeno atypiano atypia

Atypical Atypical hyperplasiahyperplasia

1.271.27 1.881.88 4.244.24

Page 5: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Cancer Prev Res 2011 Dec;4(12):1947-52.

Page 6: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

On premalignant lesionsOn premalignant lesions

““If becoming a BC results from randomly If becoming a BC results from randomly acquiring multiple mutations enabling malignant acquiring multiple mutations enabling malignant behavior (growth, motility, invasion, etc), why is behavior (growth, motility, invasion, etc), why is there an apparent order to the development there an apparent order to the development and progression of premalignant lesions?”and progression of premalignant lesions?”

D. Craig AllredD. Craig Allred

Ca Prev Res, 2011Ca Prev Res, 2011

•

Page 7: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

On premalignant lesionsOn premalignant lesions

• Incidence of premalignant lesions in non-Incidence of premalignant lesions in non-cancerous breasts declines significantly cancerous breasts declines significantly from PDWA to atypia to CISfrom PDWA to atypia to CIS

• Regions of gradual histologic continuity Regions of gradual histologic continuity between these existbetween these exist

• Premalignant lesions much more Premalignant lesions much more common in cancer-containing breasts common in cancer-containing breasts (coexistent atypia ~ 50%).(coexistent atypia ~ 50%).

Page 8: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

On premalignant lesionsOn premalignant lesions

• Atypias coexisting with DCIS and Atypias coexisting with DCIS and invasive BC share genetic alterationsinvasive BC share genetic alterations

• ~ 50% of atypias contain monoclonal ~ 50% of atypias contain monoclonal populations of cellspopulations of cells

Page 9: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

BBD: Risk PredictionBBD: Risk Prediction

Relative risks by histologyRelative risks by histology

Non-Non-proliferativeproliferative

ProliferativeProliferativeno atypiano atypia

Atypical Atypical hyperplasiahyperplasia

1.271.27 1.881.88 4.244.24

Page 10: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Atypia (ADH and ALH)Atypia (ADH and ALH)

• How well do current models work for How well do current models work for women with atypical hyperplasia?women with atypical hyperplasia?

• Does a positive family history further Does a positive family history further increase risk?increase risk?

• Can we better stratify risk within atypia?Can we better stratify risk within atypia?

• Can biomarkers stratify risk?Can biomarkers stratify risk?

Page 11: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Atypical HyperplasiaAtypical Hyperplasia

• ~ 50,000 US women diagnosed with AH ~ 50,000 US women diagnosed with AH each yeareach year

• ~ 54,000 US women diagnosed with ~ 54,000 US women diagnosed with DCIS each yearDCIS each year

Page 12: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.
Page 13: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Atypical Ductal Hyperplasia (ADH)Atypical Ductal Hyperplasia (ADH)

Within ducts, proliferation Within ducts, proliferation of monotonous cells in of monotonous cells in architecturally complex architecturally complex patterns including patterns including secondary lumens and secondary lumens and micropapillary formations.micropapillary formations.

Page 14: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Atypical Lobular Hyperplasia (ALH)Atypical Lobular Hyperplasia (ALH)

Expanded acini filled Expanded acini filled with monotonous with monotonous polygonal cells with polygonal cells with loss of acini lumens. loss of acini lumens.

Page 15: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Major Studies of Atypia and Associated Breast Cancer

Study Year Population Method of Diagnosis

Pathology Review

Median f/u (yrs)

# (%) with atypia

Breast Cancer Relative Risk

(95% CI)

Comments

Nashville 1 1985 10542 Tennessee patients with BBD 1950-1968

Surgical breast biopsy

Central review

17.5 377 (3.6%)268 women with FU (283 biopsies)

ALH 4.2 (2.6-6.9)

ADH 4.3 (2.7-6.9)

39 women with AH & FH with RR=8.9 (4.8-17) 

Nurses Health Study 2

1992 Nurses Health Study part’s with cancer or BBD, 121 cases/488 controls 

Surgical breast biopsy

Central review

9   3.7(2.1-6.8)

Risk higher in premenopausal than postmenopausal. FH does not increase risk. 

Mayo3 2005 9087 women with biopsied BBD 1967-1991

Surgical breast biopsy

Central review 

12.2 336 (3.7%) 4.4(3.4-5.6)

REF Iowa SEER

1Dupont WD, Page DL: Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 1985; 312:146-151. 2London SJ, Connolly JL, Schnitt SJ, Colditz GA: A prospective study of benign breast disease and the risk of breast cancer. JAMA 1992; 267:941-9443Hartmann LC, Sellers TA, Frost MH, et al.: Benign breast disease and the risk of breast cancer. N Engl J Med 2005; 353:229-237.

Page 16: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

  

 

Page 17: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.
Page 18: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.
Page 19: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.
Page 20: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Gail modelGail model

• Best-known model; incorporates Best-known model; incorporates multiple factors in risk calculation multiple factors in risk calculation

• Gail model on NCI website is viewed ~ Gail model on NCI website is viewed ~ 500,000 times a year500,000 times a year

Page 21: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Atypia and Gail modelAtypia and Gail model

• 331 women with atypia in Mayo BBD 331 women with atypia in Mayo BBD cohortcohort

• Median follow-up 13.7 yearsMedian follow-up 13.7 years

• 58 invasive breast cancers; 8 in the first 58 invasive breast cancers; 8 in the first five yearsfive years

Page 22: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

c-statistic 0.50 (0.44-0.55)

Pankratz et alJCO 11/08

Page 23: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Gail model features and association with Gail model features and association with breast cancer riskbreast cancer risk

CharacteristicsCharacteristics P-valueP-value

Age at biopsyAge at biopsy 0.9030.903

Age at menarcheAge at menarche 0.3980.398

Age at first live birthAge at first live birth 0.2690.269

First degree relatives with First degree relatives with breast cancerbreast cancer

0.2630.263

Number of biopsiesNumber of biopsies 0.4910.491

331 women with atypia—Mayo

Pankratz, Hartmann et al. JCO, 2008

Page 24: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

If tissue is the basis of the model . . .

In displaying the phenotype of atypia, the tissue has already integrated various risk exposures.

Page 25: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Boughey J C et al. JCO 2010;28:3591-3596

©2010 by American Society of Clinical Oncology

Cumulative risk of BC after atypiaCumulative risk of BC after atypia

Page 26: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Cumulative breast cancer incidence Cumulative breast cancer incidence among women with atypical hyperplasiaamong women with atypical hyperplasia

Bre

as

t C

an

ce

r In

cid

en

ce

3+

38%

23%

12%

5%

Page 27: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.
Page 28: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.
Page 29: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Involution (Regression)Involution (Regression)

Page 30: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.
Page 31: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.
Page 32: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

““In summary, recent work by the Mayo group In summary, recent work by the Mayo group emphasizes the emphasizes the potential for using visual potential for using visual assessmentsassessments of tissue architecture as of tissue architecture as integrated measures of riskintegrated measures of risk. .

JNCI, Nov 2010JNCI, Nov 2010

J Natl Cancer Inst (2010) 102 (22): 1685-1687.

Page 33: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

JNCI editorial, Nov 2010JNCI editorial, Nov 2010

• Improving breast cancer risk prediction Improving breast cancer risk prediction is critically important given the is critically important given the limitations of currently available modelslimitations of currently available models and the and the desirability of tailoring screening desirability of tailoring screening and preventionand prevention to levels of risk.“ to levels of risk.“

Page 34: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

No breast cancer

Breast cancer

Matched on age, era, histology

Can molecular analyses differentiate between cases and controls?

Biomarker StudiesBiomarker Studies

Page 35: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.
Page 36: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Association of cyclooxygenase-2 staining intensity in atypia Association of cyclooxygenase-2 staining intensity in atypia with risk of breast cancer *with risk of breast cancer *

COX-2 staining COX-2 staining intensityintensity

No. of women No. of women RR (95% CI)**RR (95% CI)**

All women All women 235235 3.31 (2.38 to 4.49)3.31 (2.38 to 4.49)

Staining categoryStaining category

0-1+0-1+ 130130 2.63 (1.56 to 4.15)2.63 (1.56 to 4.15)

2+2+ 7171 3.56 (1.94 to 5.97)3.56 (1.94 to 5.97)

3+3+ 3434 5.66 (2.59 to 10.75)5.66 (2.59 to 10.75)

*COX-2 = cyclooxygenase-2; RR = relative risk; CI = confidence interval

**Standarized incidence ratio and 95% confidence intervals, comparing observed number of breast cancers with those expected. All results account for age and calendar period.

Visscher DW et al, J Natl Cancer Inst 2008

Page 37: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.
Page 38: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Santisteban M et al. Breast Cancer Res Treat 2009

Page 39: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

ER Expression in AtypiaER Expression in Atypia

• 246 women with AH who had open surgical 246 women with AH who had open surgical biopsy, 49 of whom developed BC biopsy, 49 of whom developed BC

• 87 with ADH87 with ADH• 141 with ALH141 with ALH• Median F/U = 14.4 yrsMedian F/U = 14.4 yrs• Used computerized digital image analysis to Used computerized digital image analysis to

quantitate ER expressionquantitate ER expression

Page 40: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Cancer Prev Res 2011 Mar;4(3):435-44.

Page 41: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Relationship between ER expression and atypia type.

Cancer Prev Res 2011 Mar;4(3):435-44.

Page 42: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Cancer Prev Res 2011 Mar;4(3):435-44.

Page 43: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

ADH showing strong, homogeneous ER staining

Page 44: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

ALH showing moderate ER staining heterogeneously

Page 45: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Relationship between ER expression and age in women with atypical hyperplasia.

Cancer Prev Res 2011 Mar;4(3):435-44.

Page 46: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

ER Expression in AtypiaER Expression in Atypia

• ER expression did not vary by –ER expression did not vary by –

-- # of foci of atypia-- # of foci of atypia

-- Involution extent (controlling for age)-- Involution extent (controlling for age)

-- Extent of family history-- Extent of family history

Page 47: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Atypia: SummaryAtypia: Summary

• Atypia = High risk finding (RR ~ 4)Atypia = High risk finding (RR ~ 4)

• Features that do NOT further stratify Features that do NOT further stratify risk: risk: Family history Family history

Type of atypiaType of atypia

Page 48: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Atypia: SummaryAtypia: Summary

• Features that DO further stratify risk:Features that DO further stratify risk:

# of foci of atypia# of foci of atypia

extent of involutionextent of involution

younger ageyounger age

biomarkers, eg COX-2 and Ki67biomarkers, eg COX-2 and Ki67

require validationrequire validation

Page 49: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Missing ADH ALH ADH and ALH

Page 50: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Better risk prediction modelBetter risk prediction model

Clinical Risk Factors

Clinical Risk Factors

Benign HistologyBenign

Histology

BiomarkersBiomarkersMammographic

DensityMammographic

Density

Page 51: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.

Mayo BBD Mayo BBD Cohort Cohort

Breast CliniciansLynn Hartmann, MDAmy Degnim, MDKarthik Ghosh, MDJudy Boughey, MD

Basic ScienceDerek Radisky, PhD

Database Management Marlene Frost, PhD Teresa AllersJo Johnson Mary Campion Melanie Kasner

Biostatisticians Shane Pankratz, PhDRob Vierkant, MASLorelle Benetti, BARyan Frank, BA

Pathologists Dan Visscher, MDAziza Nassar, MDCarol Reynolds, MD

EpidemiologyCeline Vachon, PhD

Page 52: Benign Breast Disease – Focus on Atypia Lynn C. Hartmann, MD Women’s Cancer Program Mayo Clinic Cancer Center.
http://www.barnesandnoble.com/w/the-mayo-clinic-breast-cancer-book-mayo-clinic/1110563471?ean=9781561487721

012 hartmann comm_lpl_1962

012 hartmann comm_lpl_1962

Nicolai Hartmann's Intuitionistic Ethics - McMaster · PDF fileTitle: Nicolai Hartmann's Intuitionistic Ethics Author: John Ross King Keywords: Nicolai Hartmann, philosophy, German

Nicolai Hartmann's Intuitionistic Ethics - McMaster · PDF fileTitle: Nicolai Hartmann's Intuitionistic Ethics Author: John Ross King Keywords: Nicolai Hartmann, philosophy, German

Atypia and Differential Diagnosis in Cellular Blue Nevi ...atypia or nuclear pleomorphism. No mitosis was observed in 16 (72%) cases, while there was one mitosis per square millimeter

Atypia and Differential Diagnosis in Cellular Blue Nevi ...atypia or nuclear pleomorphism. No mitosis was observed in 16 (72%) cases, while there was one mitosis per square millimeter

Horoscopo Hartmann 2006

Horoscopo Hartmann 2006

Franz Hartmann - Geomancy

Franz Hartmann - Geomancy

Hartmann Secret-symbols Rosecrucians

Hartmann Secret-symbols Rosecrucians

HARTMANN AND KESTER’S PLANT PROPAGATION stuff/ph... · HARTMANN AND KESTER’S PLANT PROPAGATION. PRINCIPLES AND PRACTICES. EIGHTH EDITION. Hudson T. Hartmann, PhD. University of

HARTMANN AND KESTER’S PLANT PROPAGATION stuff/ph... · HARTMANN AND KESTER’S PLANT PROPAGATION. PRINCIPLES AND PRACTICES. EIGHTH EDITION. Hudson T. Hartmann, PhD. University of

Structure - Hartmann & Bender

Structure - Hartmann & Bender

WHAT ARE THESE STAINS? · IMMUNOHISTOCHEMICAL STAINS Malignant Melanoma • SSMM: Atypia: Upward spread: MART-1, S100, etc • LM: Minimal atypia high density: MITF, SOX10 > MART-1

WHAT ARE THESE STAINS? · IMMUNOHISTOCHEMICAL STAINS Malignant Melanoma • SSMM: Atypia: Upward spread: MART-1, S100, etc • LM: Minimal atypia high density: MITF, SOX10 > MART-1

Dosimetry Photon Beams - indico.ictp.itindico.ictp.it/.../4/material/slides/0.pdf · Dosimetry: Photon Beams G. Hartmann EFOMP & German Cancer Research Center (DKFZ) g.hartmann@dkfz.de

Dosimetry Photon Beams - indico.ictp.itindico.ictp.it/.../4/material/slides/0.pdf · Dosimetry: Photon Beams G. Hartmann EFOMP & German Cancer Research Center (DKFZ) [email protected]

Terahertz wavefront measurement with a Hartmann sensor · Terahertz wavefront measurement with a Hartmann ... Terahertz wavefront measurement with a Hartmann sensor ... Golay cell

Terahertz wavefront measurement with a Hartmann sensor · Terahertz wavefront measurement with a Hartmann ... Terahertz wavefront measurement with a Hartmann sensor ... Golay cell

HTAi 2015 - Profile of the effectiveness of detection of atypia by the cervical cancer screening in the municipalities of Rio de Janeiro

HTAi 2015 - Profile of the effectiveness of detection of atypia by the cervical cancer screening in the municipalities of Rio de Janeiro

ICTY Hartmann Judgment

ICTY Hartmann Judgment

Open Access Flat Epithelial Atypia: A Review of Current ... · Open Access Flat Epithelial Atypia: A Review of Current Concepts Amy L. Adams* Department of Pathology and Laboratory

Open Access Flat Epithelial Atypia: A Review of Current ... · Open Access Flat Epithelial Atypia: A Review of Current Concepts Amy L. Adams* Department of Pathology and Laboratory

HEALTH AMDG HARTMANN

HEALTH AMDG HARTMANN

Hartmann Interactions 2

Hartmann Interactions 2

Endometrial Cancer - University of Pittsburghsuper4/34011-35001/34071.ppt · PPT file · Web view2009-11-17 · Endometrial Cancer ... Hyperplasia Complex hyperplasia with atypia

Endometrial Cancer - University of Pittsburghsuper4/34011-35001/34071.ppt · PPT file · Web view2009-11-17 · Endometrial Cancer ... Hyperplasia Complex hyperplasia with atypia

CAP Cancer Protocol Endometrium · Web viewIn addition, there is nuclear atypia in the form of nuclear enlargement, pleomorphism, rounding, loss of polarity, and nucleoli.1 The diagnosis

CAP Cancer Protocol Endometrium · Web viewIn addition, there is nuclear atypia in the form of nuclear enlargement, pleomorphism, rounding, loss of polarity, and nucleoli.1 The diagnosis

Hartmann - Model Basedworking

Hartmann - Model Basedworking

Hartmann Studios, Inc.

Hartmann Studios, Inc.