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From Radical Mastectomy to Partial Breast Irradiation: The Evolution of Breast Cancer Care

From Radical Mastectomy to Partial Breast Irradiation: The Evolution of Breast Cancer Care. Johnny Ray Bernard, Jr., M.D. October 19, 2012. William Stewart Halsted. 1852: Born in New York City Sept. 23 1870: Graduates from Phillips Academy Andover 1874: Graduates Yale University

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From Radical Mastectomy to Partial Breast Irradiation: The Evolution of Breast Cancer Care

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  1. From Radical Mastectomy to Partial Breast Irradiation: The Evolution of Breast Cancer Care Johnny Ray Bernard, Jr., M.D. October 19, 2012

  2. William Stewart Halsted • 1852: Born in New York City Sept. 23 • 1870: Graduates from Phillips Academy Andover • 1874: Graduates Yale University • Enrolls in Columbia University College of Physician and Surgeons in New York • 1881: First emergency blood transfusion, performed on sister • Performs one of first operations for gallstones in U.S., performed on mother • 1882: Development of Halsted radical mastectomy • 1884: Begins cocaine research, developing the nerve block and other local anesthesia techniques. • 1889: Invention of surgical gloves

  3. William Stewart Halsted • 1889: Publishes inguinal hernia repair method at the same time as EdoardoBassini. • 1890: Appointed first Chief of Surgery at Johns Hopkins Hospital • 1892: Performs first successful subclavian artery ligation • 1893: Started the first formal surgical residency training program in the United States • 1898: American Surgical Association establishes Halsted's mastectomy and inguinal hernia repair as gold standards • 1922: Dies in Baltimore from post-op complications of bile duct surgery September 7

  4. Halsted Radical Mastectomy • Developed and first performed by William Stewart Halsted in 1882. • En bloc removal of the breast, muscles of the chest wall, and contents of the axilla

  5. Halsted Radical Mastectomy Osborne, MP. Lancet Oncol. 2007 Mar;8(3):256-65.

  6. Halsted Radical Mastectomy • The “established and standardized operation for cancer of the breast in all stages, early or late” • From 1895 to the mid-1970s, about 90% of the women being treated for breast cancer in the US underwent the radical mastectomy. Bloodgood JC. Problems of cancer. J Kansas Med Soc 1930;31:311-6

  7. What Changed? • Patient dissatisfaction with results, anecdotal information regarding other procedures, some surgeons advocating more extensive surgery, some surgeons advocating more limited operations led to controversy regarding the procedure by the mid 1960’s • Also new information about tumor spread suggested that less radical surgery might be just as effective as the more extensive operations that were being performed.

  8. National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 • To help resolve the controversy, the NSABP initiated the B-04 clinical trial in 1971 • Aim: To determine whether patients with either clinically negative or clinically positive axillary nodes who received local or regional treatments other than radical mastectomy would have outcomes similar to those achieved with radical mastectomy. Fisher B, et al. N Engl J Med. 2002 Aug 22;347(8):567-75.

  9. 1765 women (1665 in this report) with operable breast cancer were randomized between July 1971 and September 1974. No women received adjuvant chemotherapy. 87% followed for at least 25 years or were known to have died before that time.

  10. Radiation • Supervoltage equipment • Tangential fields • Node negative: 50 Gy in 25 fractions, 2Gy/fraction • Node positive: • An additional boost of 10 to 20 Gy • 45 Gy in 25 fractions, 1.8 Gy/fraction, was delivered to both the internal mammary nodes and the supraclavicular nodes Fisher B, et al. N Engl J Med. 2002 Aug 22;347(8):567-75.

  11. Definitions • Local recurrence: recurrences in the chest wall, the surgical scar, or both • Regional recurrence: recurrences in the supraclavicular, subclavicular, or internal mammary nodes or in the ipsilateral axilla of patients treated with either radical mastectomy or total mastectomy and regional irradiation • Women with negative nodes who had total mastectomy alone and who subsequently had ipsilateral positive nodes that required axillary dissection were not considered to have had a recurrence unless the nodes could not be removed Fisher B, et al. N Engl J Med. 2002 Aug 22;347(8):567-75.

  12. End Points • Calculated from the date of mastectomy • Disease-free survival: The first local, regional, or distant recurrence of tumor; contralateral breast cancer or a second primary tumor other than a tumor in the breast; and death of a woman who had no evidence of cancer • Relapse-free survival: The first local, regional, or distant recurrence or an event in the contralateral breast that was judged to be a recurrence • Distant-disease-free survival: Distant recurrences that occurred either as the first recurrence or after a local or regional recurrence, contralateral breast cancers, and other second primary cancers • Overall Survival: All deaths Fisher B, et al. N Engl J Med. 2002 Aug 22;347(8):567-75.

  13. 25yr F/U: Results-DFS • Node Negative: No significant difference (P=0.65) • 19% percent vs. 13%, RM vs. TM+XRT (P=0.49) • 19% with TM alone (P=0.39, compared to RM) • TM+XRT vs. TM alone (P=0.78) • Node Positive: No significant difference • 11% vs. 10%, RM vs. TM+XRT (P=0.20)

  14. Results-RFS • Node Negative: No significant difference (P=0.46) • 53% percent vs. 52%, RM vs. TM+XRT (P=0.74) • 50% with TM alone (P=0.27, compared to RM) • TM+XRT vs. TM alone (P=0.15) • Node Positive: No significant difference • 36% vs. 33%, RM vs. TM+XRT (P=0.40)

  15. Results Regardless of nodal status, most first events were related to distant recurrences of tumor and to deaths that were unrelated to breast cancer.

  16. Results Fisher B, et al. N Engl J Med. 2002 Aug 22;347(8):567-75.

  17. No Axillary Treatment • 68/365 women with negative nodes who underwent total mastectomy without radiation therapy (18.6%) subsequently had pathological confirmation of positive ipsilateral nodes. • Identified within 2 years after surgery in 51/68 (75%) women • Between 2-5 years in 10/68 (15%) women • Between 5-10 years in 6/68 (9%) women • Between 10-25 years in 1/68 (1%) woman • Median time from mastectomy to the identification of positive axillary nodes was 14.8 months (range, 3.0 to 134.5).

  18. Node negative: 68.3% of breast-cancer–related events occurred within the first 5 years of f/u -65.1% of these were distant recurrences, 10.3% contralateral breast cancer Node positive: 81.7% of breast-cancer–related events occurred within the first 5 years of f/u -68.1% of these were distant recurrences

  19. Results-DDFS & OS Also, no difference in distant-disease-free survival or overall survival Fisher B, et al. N Engl J Med. 2002 Aug 22;347(8):567-75.

  20. Recurrence & Contralateral Cancer The cumulative incidence of death after a recurrence or a diagnosis of contralateral breast cancer was 40% in women with negative nodes and 67% in women with positive nodes. Fisher B, et al. N Engl J Med. 2002 Aug 22;347(8):567-75.

  21. Conclusions • Similar outcomes for patients with either clinically negative or clinically positive axillary nodes who received local or regional treatments other than the gold standard Halsted radical mastectomy. • Thus, less extensive surgery can be safely performed. • No benefit for radiation in clinically node negative patients in terms of DFS, RFS, DDFS, OS vs. those with axillary node dissection • Benefit in local control vs. those without axillary treatment. • Without any axillary treatment, ~20% risk of axillary disease, less with treatment, but still no change in DDFS or OS. • Most events occurred within 5 years but long term follow-up of patients is still needed as events still occurred after 5 years. • Treatment to improve distant recurrence needed.

  22. So now we know that we don’t have to perform such extensive surgery, what about not removing the whole breast at all?

  23. Surgical Pathology • Numerous surgical series of mastectomy specimens showed that breast cancer was multifocal and multicentric in nature. • Holland, et. al. noted that of 282 mastectomy specimens with invasive cancer, 177 (63%) specimens exhibited additional cancer aside from the index tumor, with 121 (43%) specimens having tumor more than 2cm away from the index tumor. • This suggested that women undergoing breast conservation would have a significant rate of local recurrence by removing only the primary tumor. Holland R, et al. Cancer. 1985 Sep 1;56(5):979-90.

  24. NSABP B-06 • To help resolve the controversy, the NSABP initiated the B-06 clinical trial in 1976. • Aim: To determine whether women with stage I or II breast tumors that were 4 cm or less in diameter who received breast-conserving surgery would have outcomes similar to those achieved with total (new standard) mastectomy. Fisher B, et al. N Engl J Med. 2002 Oct 17;347(16):1233-41.

  25. 2163 women (1851 in this report) with invasive breast tumors that were <4 cm and with either negative or positive axillary lymph nodes (stage I or II breast cancer) were randomized between August 1976 and January 1984. Axillary nodes were removed regardless of the treatment assignment.

  26. Treatment • Lumpectomy: Removal of sufficient normal breast tissue to ensure both negative margins (no tumor at inked margin) and a satisfactory cosmetic result • Only the lower two levels of the axillary nodes were removed • +margins underwent total mastectomy but continued to be followed for subsequent events • Total Mastectomy: • The axillary nodes were removed en bloc with the tumor • Radiation: • 2Gy/fraction to 50 Gy to the breast, but not the axilla • Chemo: Any positive axillary nodes received adjuvant systemic therapy with melphalan and fluorouracil Fisher B, et al. N Engl J Med. 2002 Oct 17;347(16):1233-41.

  27. Definitions • Local recurrence: A first recurrence of a tumor in the chest wall or in the operative scar, but not in the ipsilateral breast, was classified as a local recurrence. • Ipsilateral breast recurrence after lumpectomy was considered to be a cosmetic failure since women who underwent total mastectomy were not at risk for such an event. • Regional recurrence: Recurrences in the internal mammary, supraclavicular, or ipsilateral axillary nodes were classified as regional occurrences. Fisher B, et al. N Engl J Med. 2002 Oct 17;347(16):1233-41.

  28. Endpoints • Calculated from the date of surgery • Disease-free survival: The first recurrence of disease at a local, regional, or distant site; the diagnosis of a second cancer; and death without evidence of cancer • Distant-disease–free survival: Distant metastases as first recurrences, distant metastases after a local or regional recurrence, and all second cancers, including tumors in the contralateral breast • Overall survival: All deaths Fisher B, et al. N Engl J Med. 2002 Oct 17;347(16):1233-41.

  29. 20yr F/U: Results IBTR • 14.3 % L+XRT vs. 39.2% L alone (P<0.001) • Benefit of XRT independent of nodal status • Node Neg: 17% vs. 32% (P<0.001) • Node Pos: 44% vs. 9% (P<0.001) • L+XRT Time to Recurrence • <5yrs: 40% • 5-10yrs: 29% • >10yrs: 31% • L alone Time to Recurrence • <5yrs: 73% • 5-10yrs: 18% • >10yrs: 9% Fisher B, et al. N Engl J Med. 2002 Oct 17;347(16):1233-41.

  30. Results As in B-04, the most frequent first events were distant recurrences Fisher B, et al. N Engl J Med. 2002 Oct 17;347(16):1233-41.

  31. Results-DFS No significant difference (P=0.26) 36% vs. 35% vs. 35%, TM vs. L+XRT vs. L alone

  32. Results-DDFS & OS DDFS: No significant difference (P=0.34) 49% vs. 46% vs. 45%, TM vs. L+XRT vs. L alone OS: No significant difference (P=0.57) 47% vs. 46% vs. 46%, TM vs. L+XRT vs. L alone

  33. 69% of first recurrences were detected <5yrs of surgery, 20% between 5-10yrs, and 11% after 10 years • 9% of local recurrences, 7% of regional recurrences, and 13% of distant recurrences were detected after 10 years • Contralateral breast: 38% detected <5yrs of surgery, 30% 5-10yrs, and 32% after 10 years.

  34. Recurrence & Contralateral Cancer Fisher B, et al. N Engl J Med. 2002 Oct 17;347(16):1233-41.

  35. Recurrence & Contralateral Cancer The cumulative incidence of death after a recurrence or a diagnosis of contralateral breast cancer was 40% in women with negative nodes and 67% in women with positive nodes. Fisher B, et al. N Engl J Med. 2002 Oct 17;347(16):1233-41.

  36. Conclusions • Women with early stage breast cancer who have breast conserving surgery have outcomes similar to those achieved with total mastectomy. • Radiation therapy is a critical component of breast conservation. • Breast conservation should be offered to women with early stage breast cancer. • Most events occurred within 5 years but long term follow-up of patients is still needed as events still occurred after 5 years • Treatment to improve distant recurrence needed.

  37. Pathologic Findings from the NSABP B-06 • 110 local breast recurrences were observed in 1108 pathologically evaluable patients • All 110 recurrences were noted to be in or close to the quadrant of the initial or index cancer. • The most common presentation of breast recurrence appeared to be a localized mass within or close to the quadrant of the index cancer (86%). • In 14%the recurrence not only involved the same quadrant, but was more diffuse within the breast. Fisher ER, et al. Cancer. 1986 May 1;57(9):1717-24.

  38. So now we know that BCT is feasible and most recurrences occur close to the original tumor site, what about not radiating the whole breast?

  39. Leading the Way to PBI • Other pathologic studies confirming findings • Patients not desiring weeks of radiation treatment • Phase I/II studies of accelerated WBI in 4-5 days using multi-catheter interstitial brachy • Radiation to just the tumor bed • Multi-catheter interstitial brachytherapy • Balloon catheters and 3DCRT • Strut based catheter (SAVI)

  40. 3D CRT

  41. Evolution of Brachytherapy Techniques Interstitial Balloon Strut Applicator Multi-catheter Single catheter Multi-catheter

  42. What Can Happen After a Balloon?

  43. Persistent Seroma Balloon applicators Symptomatic: 3%-46% Potential causes Contiguous V200 Tissue compression Both?

  44. Strut Based Applicator Greater flexibility Treats the widest array of cavity & breast sizes Enhanced performance Eliminates skin spacing restrictions Better outcomes Lowers toxicity & risk of persistent seroma Exceptional precision Sculpt dose with selective radiation Added convenience Simple, secure placement and removal

  45. APBI Data Review * Conclusion - Partial breast irradiation using interstitial HDR implants or EB to deliver radiation to the tumor bed alone for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with conventional WBI. Significantly better cosmetic outcome can be achieved with carefully designed HDR multi-catheter implants compared with the outcome after WBI. There have been no differences in survival with APBI compared to WBI.

  46. Strut Based Applicator Data Review

  47. Strut Based Applicator Data Review

  48. Strut Based Applicator Data Review

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