1. BREAST CANCER Anterpreet Neki, MD , MS

2. MORTALITY RATES OF CANCER IN WOMEN - 2008

3. Estimated reduction in US overall breast cancer mortality is 28-65%
IMPACT OF RESEARCH ON BREAST CANCER SCREENING
AND RISK-REDUCTION
Estimated reduction in US overall breast cancer mortality is 28-65%
(Breast cancer mortality RR >50 y and y- 0.85)
The identification of DCIS has increased 7-fold since 1980
Berry et al NEJM 2005

4. WHY HOPE ?

5. 269,800 Cancer Deaths (all sites)
SCA-14 SABCS V pptSCA-10 breast cancer slides_ ppt
12/19/2017 3:01 AM
Breast Cancer Is a Significant Public Health Concern for Women – Cancer Deaths
26% Lung and bronchus
15% Breast
9% Colon and rectum
6% Pancreas
5% Ovary
4% Non-Hodgkin lymphoma
3% Leukemia
3% Uterine corpus
2% Liver & intrahepatic
bile duct
2% Brain & other
nervous system
25% All other sites
40,170
Deaths
192, New BC Cases
269,800 Cancer Deaths (all sites)
Adapted from American Cancer Society. Cancer Facts and Figures 2009. 5

6. BREAST CANCER EPIDEMIOLOGY
-Most common cancer in women in the world
-commoner in developed nations (obesity,inactivity)
-14% of cancer deaths (second after lung CA)
-mortality decreased by 34% in last 2 decades
-black women have a lower rate of Breast CA, but relatively higher mortality

7. RISK FACTORS
-1:8
-Exogenous hormones,obesity,exercise,alcohol,diet,breast density
-Older age, female
-Earlier menarche, late menopause,late first birth,nulliparity
-Benign breast disease
-Family history (5-10%): 1 deg relative,BRCA1/2 mutations,p53
-Ashkenezi jews
-Radiation exposure

8. SCREENING
-Mammographic screening : 23% reduction in breast CA relted mortality in F yrs, and 15% decrease in mortality in yrs
-Annual mammograms and MRI in BRCA mutants starting at age 25
-Core biopsy of suspicious tissue for pathology, ER, PR, HER2
-H/o mantle radiation: annual mammogram and MRI

10. Breast Cancer: Then and Now
SCA-14 SABCS V pptSCA-10 breast cancer slides_ ppt
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Breast Cancer: Then and Now
Then
~75% of women survived ≥5 years
Mastectomy was the only surgical option
Single-agent chemotherapy was standard of care
Hormonal therapy with tamoxifen was under investigation only
Genes involved in breast cancer development have not yet been identified
Now
~90% of women survive ≥5 years
Lumpectomy is available
Combination chemotherapy is the standard of care
Hormonal therapy is widely used
Receptor-based therapy is widely used
Understanding of genetic components have expanded
National Cancer Institute. Available at: 10

11. DIAGNOSIS
Ultrasound guided core needle biopsy
ER/PR/HER2
PROGNOSIS
Size, multiple, histology, grade, lymph nodes, proliferative rate, ER/PR, Her2,Intrinsic molecular subtypes (luminalA/B, basal/triple negative)
OncotypeDx (node-,ER+)= Recurrance score
(low= do not benefit from chemo in addition to hormonal therapy)

12. STAGING
T tumors size T0-4
N Number/nature of nodes N0-3
M Metastasis M0-1
Stage TNM

14. TREATMENT
LOCAL
Surgery : Mastectomy
Lumpectomy+Radiation
Radiation
Hormonal therapy
Her2based (Herceptin, Pertuzumab),
Chemotherapy (>0.5 cm, LN+)
(doxorubicin,cyclophosphamide,taxol,etc)
METASTATIC
Palliative chemo, radiation, bone support (Zometa,Xgeva)

15. BREAST CONSERVING SURGERY
Radical Mastectomy
Modified Radical
Mastectomy
Lumpectomy

17. ONCOTYPE Dx ASSAY Distant Recurrence at 10 Years Benefit from chemo
Tam
Tam + Chemo
0.4
0.3
Intergroup Trial
For Randomization
Distant Recurrence at 10 Years
Benefit from chemo
0.2
0.1
0.0
Minimal, if any, Chemo Benefit
Clear Chemo Benefit 10 20 30 40 50
Recurrence Score
Recurrence Score
Sparano, TBCI San Antonio, 2005

18. Paik S et al. NEJM 2004

20. OLD PARADIGM: “pre-genomic era”
Breast cancer is divided into ER+, ER-
Chemotherapy:
NIH consensus conference Nov 2000:
“It is accepted practice to offer cytotoxic chemotherapy to most women … primary breast cancers larger than 1 cm (both node negative and positive, ER positive or negative)”
Hormone Therapy:
For ER +
HER 2 neu status

21. Most Important Paradigm Shift: Breast Cancer is not one disease
65-75%
“A”
Breast Cancer
Breast Cancer
ER +
ER-
“B”
HER2+
15-20%
Basaloid
15%
“Triple Negative”
BRCA 1
P53
STAGE
SIZE

22. HORMONE THERAPY SERMs Tamoxifen Fulvestrant Aromatase inhibitors
Steroidal
Exemestane
Non-steroidal
Anastrazole
Letrozole

25. ENDOCRINE RESISTANCE

26. ONCOTYPE DX ASSAY

27. Survival Improvement in Metastatic Breast Cancer Patients
SCA-14 SABCS V pptSCA-10 breast cancer slides_ ppt
12/19/2017 3:01 AM
Survival Improvement in Metastatic Breast Cancer Patients
100
Period
Period 75
Censored events
P<0.001
Survival, % 50 25 12 24 36 48 60
Months
Survival of breast cancer patients presenting with metastases at diagnosis has improved over time, strongly suggesting that improvement is related to treatment
Need to switch curve key/references
Andre F, et al. J Clin Oncol. 2004; 22(16): 27

28. SURVELLENCE
-H&P 3m for 3 yr, then 6m for 4,5 yr, then annually
-report new lumps,pain, SOB,bone pain, headaches
-genetic counselling (h/o ovarian CA, 1deg relative with Br CA<50,>/=2 first deg or sec deg relatives,bilateral,male relative with Br CA
-monthly self-exam
-annual mammogram
-pelvic exam if vaginal bleeding on Tamoxifen

29. SUMMARY
-Early diagnosis /mammogram , improved survival
-lumpectomy+radiation results in breast conservation
-prognostic new tests (OncoType Dx)call help select cases for chemotherapy
-Improved oral Hormonal agents +/-Herceptin in patients with appropriate receptors , help consolidate treatment and imrove survival
-multiple new chemo/targeted /hormonal therapy combinations to slow metastatic disease
-bone support agents available
-continued close followup ,annual mammograms