BREAST CANCER 101BREAST CANCER 101A REVIEW OF PROBLEMS,

DIAGNOSTICS, AND CLINICAL MANAGEMENT

Sabha Ganai, MD, PhDAssistant Professor of SurgerySouthern Illinois University School of Medicine

DISCLOSURES

My conflicts of interest are relevant to being a practicing surgical oncologist.

Objectives

• Provide an overview of trends in breast cancer incidence and mortality

• Review screening and diagnostic modalities important for management of breast cancer

• Discuss therapeutic approches for breast cancers

Breast Cancer

• 1 in 8 (12.3%) lifetime risk for US women– Increased from 1 in 11 in the 1970s.

CA Clin J 2014; 64: 52-62.

CA Clin J 2014; 64: 9-29.

CA Clin J 2014; 64: 9-29.

CA Clin J 2014; 64: 9-29.

Breast Cancer Incidence

CA Clin J 2014; 64: 9-29.

Breast Cancer Mortality

Breast Cancer Mortality

Breast Cancer Mortality has declined by 34% since 1990.

Incidence and Mortality

CA Clin J 2014; 64: 52-62.

Incidence and Mortality

CA Clin J 2014; 64: 52-62.

ACS Screening

CA Clin J 2014; 64: 52-62.

The Controversy…

• What are the harms of mammography?– overdiagnosis?– more anxiety?– more biopsies?– time/days off work?– more cost?

USPSTF (2009)

• Biennial Mammography ages 50-74

• “The decision to start regular, biennial screening mammography before the age of 50 years should be an individual one and take into account patient context, including the patient’s values regarding specific benefits and harms.”

Mortality Reduction

• 71% survival benefit following ACS screening guidelines beyond 23% mortality reduction achieved following USPSTF guidelines

• Additional 5 lives saved per 1000 women.

Potential Harms

• Call backs for additional imaging (anxiety)

• False-positive biopsies

• False-negative screen– Missed breast cancer (dense breasts)

• Radiation-induced breast cancer risk

• Over-diagnosis– detection of a cancer that might not otherwise

become clinically-apparent during screen

Potential Harms

• Screening women in 40s:– False-positive mammogram once every 10y– False-positive biopsy once every 149y

• Invitation to treat women in 40s in Swedish mammography studies led to 29% reduction in breast cancer mortality over 16 years

• Annual vs. Biennual Screening– Annual screening leads to 30% lower recall

rates, detection of smaller tumors, and impact on stage migration

• Screening ages 40 to 79 is more cost-effective than seat belts and airbags with regard to cost-per-life-year gained– Better than drug development

• Adherence and compliance behaviors– If women’s screening behaviors are established

earlier, adherence to screening mammography improves over time.

– Women respond to an endorsement of guidelines.

• Strategy to leave decision-making up in air does not educate on risk stratification for breast cancer

Screening Breast MRI

CA Clin J 2007; 57: 75-89.

Screening Breast MRI

CA Clin J 2007; 57: 75-89.

Screening Breast MRI

CA Clin J 2007; 57: 75-89.

Should be limited to centers with biopsy capabilities

Genetic Counseling Referral

• Early-onset breast cancer (<50y)

• Triple-negative breast cancer (<60y)

• Two breast primaries or breast and ovarian cancer

• Two or more close blood relatives with breast cancer

• Male breast cancer

• Pancreas cancer

• Clustering of other cancers

Genetic Testing

• Hereditary Breast and Ovarian Cancer Syndrome– BRCA1

• 60-80% lifetime risk breast cancer• 20-40% lifetime risk ovarian cancer

– BRCA2• 40-60% lifetime risk breast cancer (5-10% male)• 10-20% lifetime risk ovarian cancer• Pancreas and prostate cancer

Genetic Testing

• PTEN (Cowden’s Disease)• 25-50% lifetime risk breast cancer• Thyroid, endometrial, genitourinary cancers

• p53 (Li-Fraumeni Syndrome)• >90% lifetime risk breast cancer• Sarcomas, brain tumors, adrenocortical tumors,

colorctal cancers

• CDH1• 40% lifetime risk breast cancer (lobular)• Hereditary diffuse gastric cancer

Molecular Subtyping

Breast Cancer Biology

ERPRHER2

Basal-like (Triple negative)HER2Luminal (ER+)

Molecular Subtyping

• Luminal (Hormone-Receptor+)– Responsive to tamoxifen and aromatase

inhibitors

• HER2– Responsive to trastuzumab and newer

biologic therapies

• Basal-like (“Triple-negative”)

Triple Assessment

• Clinical Exam– H&P

• Imaging– Diagnostic mammography / ultrasound

• Pathology– Core needle biopsy

Biopsy

• Stereotactic Core Needle Biopsy• Ultrasound-guided Core Needle Biopsy

– If Cancer, should get ER/PR/HER2 IHC

• Surgical (Excisional) Biopsy– Non-concordant results– Atypia on a core biopsy

• Sampling error (10-20%)

– Papillary lesions, radial scars

Surgical Management in 1900s

• William Stewart Halsted

• Halsted Mastectomy– Radical extirpation of

breast with pectoralis andlymph nodes

• Predicated on notion that breast cancer spreads locallyand regionally via lymphatics

Paradigm Shift

• Bernard Fisher– 1967 – Chairman of

National Surgical AdjuvantBreast and Bowel Project(NSABP)

Paradigm Shift

• Bernard Fisher– “because operable breast

cancer is a systemic disease involving a complexspectrum of host-tumorinterrelations, local-regionaltherapy is unlikely to affectsurvival.”

“Before 1971, if you had breast cancer, chances are you’d have to get your breast cut off. Surgeons had been taught one thing: radical surgery saves lives. It was Bernard Fisher who changed their minds, getting reluctant breast surgeons to enter their cancer patients into clinical trials that tested less aggressive surgery against the Halsted radical mastectomy. ”

NSABP B-04

NSABP B-06

Lowdown

• Breast-conserving therapy (lumpectomy + whole-breast radiation) and Mastectomy have similar overall survival benefit– Includes Triple-negative cancers– Goal is “clear-at-ink” negative margins

• 2014 SSO/ASTRO guidelines

• Mastectomy should be paired with referral to a Plastics/Reconstructive Surgeon

Oncoplastic Techniques

• Mastectomy– Nipple-sparing and Areola-sparing

skin-sparing approaches

• Partial Mastectomy– Various approaches accounting for location,

volume and aesthetic considerations

What about the Axilla?

Axillary Complications

ACOSOG Z0011

• Only applies to cT1-2N0 patients undergoing breast conserving surgery with radiotherapy– Observation is acceptable for SLN+ patients

• If SLN+ after mastectomy, Axillary Lymph Node Dissection is still recommended

OncotypeDX

• 21-gene RT-PCRrecurrence score

• Performed on paraffin-embeddedspecimens

• Developed and validated on patient tumor blocks from NSABP B-14 (TAM vs. Obs) and B-20 (TAM vs. Chemo/TAM)

Hormonal Tx

Hormonal Tx

Hormonal Tx

Add Chemo

The Future• Neoadjuvant Clinical Trials

– Chemo before surgery– Assessment of response to therapy

• Evolving role of surgical management of axilla– Bigger surgery does not cure bad biology

• Optimal screening paradigm in context of better imaging strategies and therapies will need to be determined– An individualized approach?

Questions?