1. Breast Conserving Therapy for The Treatment of Early Stage Breast Cancer
Nicolas Ajkay, MD, FACS
Assistant Professor of Surgery
Hiram C. Polk Jr. MD, Department of Surgery
University of Louisville School of Medicine
Director, Breast Multidisciplinary Clinic
James G Brown Cancer Center
Louisville, Kentucky

2. Faculty Disclosure
Nothing to disclose

3. Educational Need/Practice Gap
Gap = Mastectomy rates are increasing while lumpectomy rates are decreasing.
McGuire KP, et al. Ann Surg Oncol  :

4. Objectives
Upon completion of this educational activity, you will be able to:
Discuss evidence supporting breast conservation therapy for the treatment of early stage breast cancer.
Explain how to apply different surgical techniques to maximize the use of breast conservation therapy.
Identify patient and surgeon related factors that increase mastectomy rates.

5. Expected Outcome
Consider offering breast conserving therapy (BCT) for all early stage breast cancer patients.

6. 1970 2016 Radical Mastectomy Nipple sparing mastectomy
Breast Conservation therapy

7. EXTENT OF LOCOREGIONAL THEPARY FOR INVASIVE CARCINOMA
WILLIAM STEWART HALSTED
BERNARD FISHER, MD
Extent of surgery appeared to influence outcome
Breast cancer is a systemic disease from inception

8. No Systemic Adjuvant Therapy (1971-1974)
NSABP B-04
Primary Operable Potentially Curable Breast Cancer
Clinically Node Negative
Clinically Node Positive
Halsted Radical
Mastectomy
(includes axillary
dissection)
389
Total Mastectomy
+ Radiation
386
Total Mastectomy
(ALND if recurrence)
384
Halsted Radical
Mastectomy
(includes axillary
dissection)
301
Total Mastectomy
+ Radiation
305
No Systemic Adjuvant Therapy ( )
Fisher, et al. Cancer 1977;39:2827‐2839

9. NSABP B-04
No SS difference in distant disease free survival or overall survival for N- and N+ (25 year follow up).
Fisher, et al. New Engl J Med 2002;347:567‐575

10. NSABP B-06 N+ : Melphalan and 5-FU (1976-1984)
Clinical tumor size <4.0 cm, LN+/- (N=2163)
Mastectomy +
Axillary dissection
(Radical Mastectomy)
Lumpectomy +
Axillary dissection
Lumpectomy +
Axillary dissection
XRT
N+ : Melphalan and 5-FU ( )
Mastectomy if lumpectomy margins positive
Negative margins = “no ink on tumor”
Fisher, et al. New Engl J Med 2002;347:

11. NSABP B-06 Ipsilateral breast recurrence (at 20 years of FU):
Lumpectomy alone: 39.2%
Lumpectomy +XRT: 14.3%
Mastectomy: 10.2%
Cumulative incidence of 1st. ipsilateral rec.
Fisher, et al. New Engl J Med 2002;347:

12. Fisher, et al. New Engl J Med 2002;347:1233-41
NSABP B-06
No significant differences in DFS, DDFS or OS between mastectomy and lumpectomy with or without XRT, despite differences local control.
Fisher, et al. New Engl J Med 2002;347:

13. Breast Conserving Therapy
BCT (lumpectomy and radiation) is the preferred local therapy for early stage breast cancer.
Issues:
Margins
Localizing non palpable disease
Poor breast to tumor ratio
Adjuvant radiation

14. Mastectomy vs.. Breast Conservation
Prospective, Randomized Trials Comparing Mastectomy and Axillary Dissection to Breast-Conservation Therapy

15. LUMPECTOMY MARGINS Margins meta-analysis: 33 studies (1965 – 2013)
28,162 patients (1,506 had local recurrence)
Odds ratio for Local Recurrence:
OR 1.96 for positive/close vs.. negative; (p < 0.001)
Margin distance : >0 mm vs.. 1 mm (referent) vs.. 2 mm vs.. 5 mm (p = 0.12)
Houssami, et al. Ann Surg Oncol Mar;21(3):717-30

16. LUMPECTOMY MARGINS SSO-ASTRO CONSENSUS GUIDELINES
“The use of no ink on tumor as the standard for an adequate margin in invasive cancer in the era of multidisciplinary therapy is associated with low rates of IBTR and has the potential to decrease re-excision rates, improve cosmetic outcomes, and decrease health care costs.”

17. “NO INK ON TUMOR” CONSENSUS
Positive margins (ink on tumor) are associated with a two-fold increase in the risk of IBTR compared to negative margins.
Increased risk is not mitigated by favorable biology, endocrine therapy or a radiation boost.
More widely clear margins than no ink on tumor do not significantly decrease the rate of IBTR, specially for:
Young patients
Unfavorable biology
Lobular cancers
Extensive intra-ductal component.

18. EFFECT OF MARGINS CONSENSUS GUIDELINE ON RE-EXCISIONS
Variable
Pre consensus (n=124)
Post consensus
(n=42)
p value
Re-excisions, n (%)
40 (32%)
1 (2%)
<0.0001
Lumpectomy, n
27 (22%)
Mastectomies, n
13 (10%)
Heidrich et al, ASBS 2016

19. LOCALIZING NON-PALPABLE TUMORS
Wire localized lumpectomy
Radioactive seed localized lumpectomy

20. RADIOACTIVE SEED LOCALIZATION
Radioactive I125 impregnated titanium seed
Implanted1-5 days prior to surgery
Detected with SLNB probe (I125)
Less severe pain
Increased convenience for patients
No differences in volume of lumpectomy specimen or rate of positive margins
Improves surgical scheduling
Bloomquist, E et al. Breast J Mar-Apr;22(2):151-7, ASBS 2014

21. INTRAOPERATIVE ULTRASOUND AND SPECIMEN RADIOGRAPHY

22. ONCOPLASTIC SURGERY

23. Neoadjuvant Chemotherapy and Endocrine Therapy
MRI pre Neoadjuvant chemotherapy
Clip
MRI post Neoadjuvant chemotherapy

24. LUMPECTOMY WITH/WITHOUT XRT
XRT decreases the risk of local recurrence after lumpectomy by 2/3

25. EFFECT OF RADIOTHERAPY ON BREAST CANCER SURVIVAL
One breast cancer death was avoided by year 15 for every four recurrences avoided by year 10, 1:4
EBCTCG, Lancet. 2005;366(9503): (meta-analysis)

26. Radiation therapy is time intensive:
WBI = 6.5 weeks of daily treatment

27. ALTERNATIVES TO WHOLE BREAST IRRADIATION
Hypofractionation: Canadian Protocol (6 vs.. 4 weeks)
50/25 vs /16 Gy, 1234 patients T1,T2,NO
No difference in LR, OS,DFS or cosmetic outcome.
Accelerated Partial Breast Irradiation: (1week BID)
Whole breast vs.. APBI NSABP B-39 – ONGOING
Whole breast 42.5/16 vs.. 3D-CRT APBI 38.5/10 BID RAPID
No difference in local control with worse cosmetic outcome
Intraoperative Radiation Therapy: (1 dose 21Gy)
WBI vs.. IORT:
TARGIT (1.3 vs.. 3.3%, p=0.042, 5 years FU)
ELLIOT (0.4 vs.. 4.4%, p<0.001, 5 years FU)
Higher local recurrence with IORT, no difference in survival.

28. CALGB 9343 – Avoidance of XRT
>70 yo
T1N0
ER(+)
BCT
(-) Margins
N=636
Tamoxifen +
XRT
317
Tamoxifen
319
10 year FU
2% LRR, OS 67%
10% LRR, OS 66%
0% AxR (no ALND)
3% AxR (no ALND)
Hughes et al, J Clin Onc 2013; 31:

29. BREAST MRI
Sensitivity for invasive cancer 88-95%, specificity 37-97%.

30. Breast MRI for newly diagnosed BC
Randomized controlled trials:
COMICE:
MRI vs.. no in breast cancer treated with lumpectomy.
No difference in re-excision rates (19% for both groups).
MONET:
MRI vs.. no in non palpable breast cancer.
Increased re-excision rate in MRI group (34 vs.. 12%).
Meta-analysis of the effect of preoperative MRI vs. standard preoperative assessment
MRI significantly increases mastectomy rates.
No difference in re-excision rates (11% for both groups)
Houssami et al, Ann Surg 2013

31. BREAST MRI FOR NEWLY DIAGNOSED BREAST CANCER
Retrospective study of 756 women (30% had MRI).
No difference in RFS (3% with MRI vs.. 4% without MRI) or OS (94% vs.. 95%) at 8 years.
Solin et al, JCO 2008:26(3):386-91

32. Time Interval (TI) From Diagnosis to Surgery
Median TI increased from compared to (35 vs.. 30 days, p <0.001).
Independent predictors of TI >30 days included patients undergoing mastectomy (with or without reconstruction), MRI use, and age.
Patient demographics, tumor biology and stage do not influence TI, while choice of surgery and MRI use are associated with longer TI.
Mariella et al, SSO 2016

33. THANK YOU