1. Local Management of Invasive Breast Cancer
By Steven Jones, MD

2. Connecting with the patient is the best part of medicine.
We’re artists, not engineers

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

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

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

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

7. 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

8. Staging Recommendation prior to primary therapy
History and physical
Liver function tests
Breast imaging: ipsilateral and contralateral breasts
Mammogram
U/S
MRI
Axillary imaging

9. MRI for Local-regional Staging
Pros:
Cons:
Changes surgery 20%
Multifocal- 3.6%
Multicentric – 4.4%
Contralateral – 1.8%
With adjuvant therapy local failure low – 6%
Too many mastectomies
Some data demonstrate no difference in local failure rates

10. MRI Pre-op Diagnostic dilemma
BRCA 1 / 2 known or suspected carriers wishing BCT
Occult malignancy presenting with axillary mets

11. Staging Recommendation Prior to Primary Therapy

12. 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)

13. 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

14. Evolution of Breast Cancer
“Cancer of the breast spreads centrifugally.
It disseminates to bone by way of the lymphatics, not by blood vessels.”
Halsted, WS. The results of radical operations for the cure of carcinoma of the breast. Ann Surg 1907; 66:1

15. Halstedian concept did not apply
More extensive surgical procedures did not reduce risk of distant metastasis
Identification of small breast cancer by mammography

16. 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

17. 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

18. 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

19. 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.

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

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

22. Margins Clear: tumor not touching the ink
Close: < 1mm – may be a problem with young or extensive intraductal component

23. 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

24. Radiation Therapy Whole breast with boost to tumor bed standard
Accelerated partial breast irradiation
Balloon ( Mammosite)
Interstitial brachytherapy
External beam limited RT
Intraoperative limited RT

25. Post-mastectomy Radiation
Early studies showed increased mortality
Recent studies show substantial decrease in locoregional recurrence
Recent trials show survival benefit 5-8% at > 10 years.

26. Indications for Post-mastectomy Radiation
T3 or T4 tumors
Tumors invading skin or muscle
4 or more pos. axillary nodes
(Some recommend for 1-3 nodes, depending)

27. Breast Reconstruction
Immediate – skin sparing
Delayed immediate – skin sparing
Delayed

28. Skin Sparing Mastectomy
Includes areolar (nipple sparing controversial)
Excise biopsy incision
Radiate positive margins

29. 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%)

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

31. Locally Advanced Cancer
Large primary tumors (>5cm) especially with pos. nodes
Tumors with skin or chest wall involvement
Tumors with fixed or matted axillary nodes or ipsilateral subclavian or supraclavicular lymph nodes
Most have been present for months or years but treatment has been delayed

32. Inflammatory Breast Cancer
Rapid onset and progression over weeks to months
Skin often discolored red to purple
Skin thickened or peau d’ orange
Induration
Invasion of dermal lymphatics is a common feature but not required or sufficient for a diagnosis
1-5% of breast cancers

33. Neoadjuvant Chemotherapy Preoperative Systemic Therapy
aka
Preoperative Systemic Therapy
Primary Chemotherapy

34. 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 downsize to allow conversion from mastectomy to BCS

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

36. Pre-operative Endocrine Therapy
Best for large low grade ER pos. tumors in post menopausal women
Response times 3 months or longer
Greater response with aromatase inhibitors compared with tamoxifen
Under-utilized in the US

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