Radiotherapy in Carcinoma of the Breast

1. Radiotherapy in Carcinoma of the Breast Patrick S Swift, MD Director, Radiation Oncology Alta Bates Comprehensive Cancer Center Berkeley, CA

2. Breast Conserving Therapy BCT • 70-80% of patients with stage I or II disease are candidates for BCT • 6 major randomized trials comparing mastectomy to BCT • No difference in DFS • No difference in OS

3. Distant Failure

4. Overall Survival

5. Absolute Contraindications to BCT • Repeatedly positive margins • Multicentric disease ( >2 quadrants) • Diffuse malignant calcifications on mammogram • Prior RT to breast • Pregnancy

6. Relative Contraindications to BCT • History of scleroderma • Large tumor in small breast • Cosmetically undesirable

7. NOT contraindications to BCT • Age • Skin or nipple retraction • Histology other than IDC • Extensive intraductal component • As long as margins are clear • Positive nodes • Location of primary in breast • Positive family history

8. Positive Margins after Lumpectomy • Single most important predictor of local failure in BCT • Consider re-excision to get negative margins • Focal positivity - may be okay • Especially if chemo or HT given • Extensive positivity - re-excise!

9. Extensive Intraductal Component (EIC) • Intraductal component a prominent part of the main tumor • Intraductal carcinoma extends BEYOND the infiltrating margin of the mass • Of uncertain significance if margins are clearly negative

10. Treatment by Stage

11. DCISDuctal Carcinoma in Situ • MRM is acceptable • no node dissection • BCT is an acceptable approach if: • Lesion is small (< 3 cm) • Margins must be negative • preferably > 10 mm in all dimensions • Nuclear grade is low to intermediate • Adjuvant radiotherapy can be delivered • S alone can be considered if margins >10 mm • controversial

12. NSABP-17 • 814 pts. with DCIS, negative margins • Randomized to RT v no RT • 50 Gy to entire breast, no boost • At 12 years, local failure rates • 31.7% for no RT • 15.7% for RT • Only comedo necrosis was a significant factor predicting for local failure

13. EORTC 10853 • 500 pts with DCIS, clear margins • Randomized to 50 Gy whole breast or no RT • At 4.25 years, local failure • 16% no RT • 9% with RT (p=0.005)

14. UKCCCR DCIS Working Group • 1030 pts with DCIS, clear margins • S alone • S + Tam • S + RT • S + RT + Tam • At 4.4.years, local failure • 14% in no RT • 6% in RT arm • S + Tam intermediate

15. Radiation TechniqueDCIS • Opposed tangential fields • Breast only • No boost • 1.8-2.0 Gy daily to 50 Gy • 2.65 Gy daily to 40 Gy

18. Van Nuys Prognostic Index Scores of 3-4 - 98% local control without RT Scores of 5-7 - 32% failed without RT, 16% with RT Scores of 8-9 - 100% failure without RT, 60% with RT

19. Radiation TechniqueT1-2 N0 • Opposed tangential fields • Breast only • Boost optional • 50 Gy in 25-28 fractions • 42.5 Gy in 16 fractions (Canadian)

20. ASTRO 2008 Plenary 42.5 Gy in 16 fractions v. 50 Gy in 25 fractions

21. ASTRO 2008 Plenary • Canadian Trial 1993-1996 • N= 1234 women • Median followup - 12 years • Local recurrence at 10 years - 6% • Excellent cosmesis at 10 yrs - 70% • No difference between 16 and 25 fractions

23. If getting chemotherapy… • Radiation is usually withheld until after the systemic therapy is complete • Delay of up to 4-6 months from surgery generally not considered a problem • Possible problem with inflammatory cancer or other locally aggressive cancers • Hypofractionated schemes may allow for early RT while waiting for Oncotype

24. Surgery alone without RT? • Meta-analysis results • Lancet. 2005 Dec 17, vol. 366(9503):2087-106 • “Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials.” • An average of 75% reduction in local failure rates with the addition of RT, in even the lowest risk groups. • A survival benefit was seen in the meta-analysis

25. Surgery alone without RT? • One possible subset may benefit • Patients > 70 years of age • with small ER+ tumors • who will get tamoxifen • No survival benefit with RT

26. Radiation TechniqueT3-4 (after neoadjuvant chemo) • Opposed tangential fields • Boost • 10 Gy for neg margins • 18 Gy for positive or close margins • 50 Gy in 25-28 fractions

27. Nodal Irradiation • N0 - no role for axillary RT • N+ • 1-3 nodes, “adequate sampling” - no RT • > 4 nodes, RT to SCLV and axilla • IM Nodal RT • > 4 axillary nodes positive • Medial T3 tumors with any nodes positive axilla • Awaiting results of two large trials (France and EORTC)

28. Full SCLV Field

29. IM Nodal Radiation Technique

31. Post-mastectomy RT • Indications • T3 lesions with any positive nodes • Smaller lesions with > 3 nodes • T4 lesions • Pectoralis fascia involvement • Technique • Tangential beams for the chest wall • Axillary/SCLV coverage • IM node coverage for medial lesions or > 3 nodes positive

32. Post-MRM RT Trials(all with chemo and modern RT)

33. RT Complications • Lymphedema • After full axillary dissection + RT - 37% • Level I/II dissection + RT - 7% • Rib fracture - 1.8% • Pneumonitis - 1-5% • Cardiac toxicity - avoidable • Radiation-induced sarcoma • 0.78% at 30 yrs.

34. Reducing Risk • Respiratory Gating • IM nodal techniques • IMRT

39. Partial Breast Irradiation • RTOG / NSABP Trial comparing • Standard whole breast RT • 3D conformal technique • Mammosite • Interstitial Implant technique • 5 days, twice daily radiation • Outcome results pending