Transcript BREAST CANCER 101 A REVIEW OF PROBLEMS, DIAGNOSTICS, AND CLINICAL MANAGEMENT

BREAST CANCER 101
A REVIEW OF PROBLEMS,
DIAGNOSTICS, AND
CLINICAL MANAGEMENT
Sabha Ganai, MD, PhD
Assistant Professor of Surgery
Southern Illinois University School of Medicine
My conflicts of interest are relevant to being a practicing
surgical oncologist.
DISCLOSURES
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 costeffective 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
Should be
limited to
centers
with biopsy
capabilities
CA Clin J 2007; 57: 75-89.
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
ER
PR
HER2
Basal-like (Triple negative)
HER2
Luminal (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 and
lymph nodes
• Predicated on notion that
breast cancer spreads locally
and regionally via lymphatics
Paradigm Shift
• Bernard Fisher
– 1967 – Chairman of
National Surgical Adjuvant
Breast and Bowel Project
(NSABP)
Paradigm Shift
• Bernard Fisher
– “because operable breast
cancer is a systemic
disease involving a complex
spectrum of host-tumor
interrelations, local-regional
therapy is unlikely to affect
survival.”
“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-PCR
recurrence score
• Performed on
paraffin-embedded
specimens
• 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?