1. Breast Cancer
Steven Jones, MD

2. Mammary Gland Anterior view Breast Anatomy
Parasternal (internal thoracic) nodes
Subclavian (apical axillary) nodes
Interpectoral
(Rotter’s) nodes
Central axillary
nodes
Brachial
(lateral axillary)
Subscapular
(posterior axillary)
Pectoral
(anterior axillary)
Breast Anatomy

3. Mammary Gland Anterior view Breast Anatomy Areola
Lobar/Lactiferous duct
Lobular duct
Breast Anatomy
Lobule
Ampulla
Nipple
Areola gland
Fat
Areola

4. Lobar/Lactiferous Duct Cross Section

5. Lobar/Lactiferous Duct Cross Section
Atypical Ductal Hyperplasia (ADH)
Excess growth within the duct includes abnormal or atypical cells. The presence of this condition increases the risk of developing breast cancer.

6. Lobar/Lactiferous Duct Cross Section
Ductal Carcinoma In Situ (DCIS)
The entire duct may be filled with abnormal, atypical cells. This condition is actually an early breast cancer.

7. Cancer cells that break out of the duct and invade the breast tissue.
Lobar/Lactiferous Duct Cross Section
Invasive Ductal Carcinoma (IDC)
Cancer cells that break out of the duct and invade the breast tissue.

8. Excess growth in the lobules
Lobular Hyperplasia
Lobular
Hyperplasia
Excess growth in the lobules
Atypical Lobular Hyperplasia
Atypical lobular hyperplasia may also develop.
If atypical lobular hyperplasia progresses in severity a condition referred to as Lobular Carcinoma In Situ (LCIS) may develop.

9. Epidemiology of Breast Cancer
232,340 American women diagnosed each year.
39,620 die each year from the disease
Lifetime risk through age 85 is 1 in 8, or 12.5%
2nd leading cause of cancer deaths among US women, after lung cancer
Leading cause of death among women age 40-55

10. Breast Cancer Causes
Hormonal factors – early menarche, late menopause, age of 1st pregnancy, HRT with progesterone
Environment, lifestyle, and diet – ionizing radiation increase risk

11. Breast Cancer Risks Gender – 1% male
Age - < 30 – rare ; risk rises sharply after 40
Personal Hx – 0.5-1% per yr in contra breast
Family Hx % of Br Ca have + fm hx; only 5-10% have an inherited mutation

12. Breast Cancer Risks
Benign Breast disease – Atypical ductal hyperplasia – RR
Lobular Carcinoma in Situ – RR, 1% per year.

13. CRITERIA FOR REFERRAL FOR GENETIC COUNSELING OF INDIVIDUALS AT INCREASED RISKFOR BRCA1/2-ASSOCIATED HEREDITARY BREAST CANCERa,b
Personal history of breast cancer diagnosed≤ 40
Personal history of breast cancer diagnosed≤ 50 and Ashkenazi Jewish ancestry
Personal history of breast cancer diagnosed≤ 50 and at least one first- or second-degree relative with breast cancer ≤50and/or epithelial ovarian cancer
aClose relatives of individuals with the history mentioned in the table are appropriate candidates for genetic counseling. It is optimal to initiate testing in an individual with breast or ovarian cancer prior to testing at-risk relatives.
bCriteria modified from NCCN (109)

14. Continued….
Personal history of breast cancer and two or more relatives on the same side of the family with breast cancer and/or epithelial ovarian cancer
Personal history of epithelial ovarian cancer, diagnosed at any age, particularly if Ashkenazi Jewish
Personal history of male breast cancer particularly if at least one first- or second-degree relative with breast cancer and/or epithelial ovarian cancer
Relatives of individuals with a deleterious BRCA1/2mutation

15. High Risk Patients
Gail model
Chemo prevention
Increased surveillance

16. Report Organization 1 2 3 4 5 Category Assessment Recommendations1 2 3 4 5
Incomplete assessment
Additional imaging evaluation
Negative
Benign finding
BI-RADS™
Probably benign
Short interval follow-up
Suspicious
Biopsy should be considered
Highly suggestive
of malignancy
Appropriate action to be taken

17. Pathological Variables
Luminal A
HER2-Positive (IHC) 12
ER-Positive(IHC) 96
Grade III 19
Tumor size> 2 cm 53
Node- positive 52

18. Pathological Variables
Luminal B (%)
HER2-Positive (IHC) 20
ER-Positive(IHC) 97
Grade III 53
Tumor size> 2 cm 69
Node- positive 65

19. Pathological Variables
HER2-like (%)
HER2-Positive (IHC)
100
ER-Positive(IHC) 46
Grade III 74
Tumor size> 2 cm
Node- positive 66

20. Pathological Variables
Basil-like (%)
HER2-Positive (IHC) 10
ER-Positive(IHC) 12
Grade III 84
Tumor size> 2 cm 75
Node- positive 40

21. Open Surgical Biopsy Biopsy Options Performed in the Operating Room
An incision is made in the breast and a large tissue sample is cut and removed
In some cases, a wire is inserted into the breast to aid in localizing the abnormality
Possible scarring and disfiguration that can interfere with future mammograms
More costly than other biopsy methods
Biopsy Options

22. Fine Needle Aspiration (FNA)
Can be performed in an outpatient setting or doctor’s office
No anesthesia
No sutures
Several needle insertions to collect fluid and/or cellular material
Cyst aspiration for fluids
Unable to mark biopsy site
Biopsy Options

23. Core Needle Biopsy Local anesthesia No sutures
Can be performed in an outpatient setting or doctor’s office
Local anesthesia
No sutures
4 – 6 needle insertions to collect a sufficient amount of breast tissue for an accurate diagnosis
Unable to mark biopsy site
Biopsy Options

24. National Surgical Adjuvant Breast Project
Radical mastectomy vs
Simple mastectomy with axillary irradiation
Simple mastectomy with delayed axillary dissection
Started in 1971, 1665 patients enrolled, 25 year follow up
No difference in disease free or overall survival

25. Breast Cancer Multifocality Holland et al.
Only 37% of cancers are confined to the primary tumor.
20% have additional cancer within 2 cms.
43% have additional cancer beyond 2 cms.
Holland R, Veling S, Mravunac M, et al. Histologic multifocality of Tis, T1-2 breast carcinomas: implications for clinical trials of breast-conserving treatment. Cancer 1985; 56: 979

26. NSABP B-06
Total mastectomy vs lumpectomy vs lumpectomy plus irradiation
No significant difference in survival
14.3% recurrence in lumpectomy plus radiation group at 25 years
39.2% recurrence in lumpectomy without radiation group at 25 years

27. Conclusion NSABP B-06
Lumpectomy followed by breast irradiation is the appropriate therapy for women with breast cancer, provided that the margins of resected specimens are free of tumor and an acceptable cosmetic result can be obtained.

28. Contraindications for Breast Conserving Therapy
Absolute:
Prior radiation to the breast or chest wall
Pregnancy
Muticentric disease
Diffuse, malignant appearing microcalcifications

29. Relative Contraindications for BCT
History of collagen vascular disease
Very large tumor > 5cms
Very large breasts

30. Axillary Biopsy and Control
1. Staging
In the absence of distant mets number of positive lymph nodes is the most important prognostic factor.
2. Regional Control
In clinically negative axilla, axillary dissection reduces local occurrence from 20% to 3%
3. Small survival advantage (3-5%)

31. Sentinel Lymph Node Technetium labeled sulfur colloid
Isosulfan blue (lymphazurin 1%)
Combined – 97% ID’ed; 6% false negative
1% anaphylactic reaction to blue dye

32. Sentinel Lymph Node Technetium labeled sulfur colloid
Isosulfan blue (lymphazurin 1%)
Combined – 97% ID’ed; 6% false negative
1% anaphylactic reaction to blue dye

33. Systemic Therapy Cytotoxic chemotherapy
Hormonal therapy – 50% reduction of recurrence, 26% reduction in mortality
Targeted therapy - Herceptin – 50% reduction of recurrence.

34. ALGORITHM FOR ADJUVANT SYSTEMIC THERAPY FOR BREAST CANCER
ER- and/or PR-Positive
ER- and PR-Negative
ERBB2 negativea
Endocrine therapy± chemotherapy
depending on risk
Chemotherapy
ERBB2 positive
Endocrine therapy+ chemotherapy+ trastuzumab
chemotherapy+ trastuzumab
ER, estrogen receptor; PR, progesterone receptor
aFormerly HER-2

35. NSABP B-18 Started 1988; 1523 pts, 4 cycles AC 80% overall response
13% pathologic complete response
No difference in overall survival
Only 3% had progression of disease
25% downstaging at axilla
30% of women will downstage to allow conversion from mastectomy to BCS

36. Indications
To downstage women with large tumors that cannot undergo BCS with good cosmetic result – 30% of women will downstage.
Early initiation of systemic treatment
In vivo assessment of response, good biological model
Less radical surgery needed

37. Tulane surgery:“ tough as the marines except the marines get to eat”