Multiple ipsilateral breast cancers: Can the breast be preserved?

Thanks to modern imaging, clinicians are finding more occult breast disease and are now increasingly facing the dilemma of how best to treat multiple cancers within the same breast.1 Multiple ipsilateral breast cancers (MIBCs) are now detected at rates ranging from 13 to 75 percent, and this uptick in detection is thought to be one of the reasons for the national and international trend toward increasing mastectomy rates.2-4 Whereas the practical solution for most surgeons and patients has been to proceed with mastectomy, perhaps it is time to consider whether treatments used to preserve the breast for one cancer can be extended to patients with two or three tumors within the same breast.

Many surgeons recommend mastectomy for women with multiple tumors due to concerns about the high rates of local recurrence. Although it is historically well-founded, this belief is based on retrospective studies from the late 1980s and early 1990s—studies that were less inclusive of current multimodality practices.5-7 Older studies on this topic reported alarming rates of local recurrence for patients with multiple tumors, but they did not include many of the current-day therapies, such as adjuvant and neoadjuvant endocrine, chemo, and radiation therapy.

More current studies have concluded that local recurrence rates in women with MIBC who have negative surgical margins and are subsequently treated with appropriate adjuvant therapy are equivalent to local recurrence rates in women with unifocal disease.8-12 The largest of these trials, conducted by Gentilini and colleagues, reviewed 476 patients treated with breast-conserving therapy (BCT) for MIBC between 1997 and 2002.9

Despite significant nodal disease in the study population (55 percent of all patients were node positive), the local recurrence rate in this trial was 5.1 percent at five years. These results are considered equivalent to recurrence rates in the unifocal breast cancer population. Because breast conservation is associated with improved patient satisfaction, quality of life, and body image compared with mastectomy, we propose it is time to revisit the practice of mastectomy in this population.

ACOSOG Z11102 is a recently activated Alliance for Clinical Trials in Oncology study that will determine prospectively whether breast conservation is a safe surgical approach for patients with MIBC. It is a single-arm trial with a primary endpoint of local recurrence. Secondary endpoints include rate of conversion to mastectomy due to persistently positive margins, inability to achieve radiation dose constraints due to volume of boost, or poor cosmesis. Additional endpoints include patient and physician perceptions of breast cosmesis, incidence of breast lymphedema, and adverse effects of radiation given larger or multiple lumpectomy cavities and boost areas.

Patients eligible for this study must meet the following criteria:

  • Older than 40 years of age
  • Greater than two foci of biopsy-proven breast cancer separated by > 3 cm of normal breast tissue
  • Largest single tumor focus < 5 cm
  • Invasive breast cancer or ductal carcinoma in situ, with minimum of one site with invasive disease
  • Biopsy-proven disease at two sites within the same breast
  • Mammogram < 60 days and magnetic resonance imaging < 45 days prior to registration
  • cN0 or N1 disease
Z11102 trial schema

Z11102 trial schema

The schema for the trial illustrates that it is a registry (non-randomized) trial. (See figure.)

This trial is the first prospective look at this increasingly common clinical scenario. Results will provide important data with which surgeons and radiation oncologists may inform patients and discuss surgical treatment options. If local recurrence rates are shown to be acceptable for BCT in women with MIBC, rates of breast conservation in this population can safely increase.

Surgeons interested in opening this study are directed to the Cancer Trials Support Unit website, where all protocol documents are available, or contact Wendy Lindeman (lindeman.wendy@mayo.edu), Kari Rosenkranz (Kari.M.Rosenkranz@hitchcock.org), or Judy Boughey (boughey.judy@mayo.edu).


References

  1. Bedrosian I, Nelson H. The paradox of breast MRI: Does finding occult disease make a difference? Bull Am Coll Surg. 2012;97(10):57-59.
  2. Bendifallah S, Werkoff G, Borie-Moutafoff C, Antoine M, Chopier J, Gligorov J, Uzan S, Coutant C, Rouzier R. Multiple synchronous (multifocal and multicentric) breast cancer: Clinical implications. Surg Oncol. 2010;19(4):e115-123.
  3. Katipamula, R, Degnim AC, Hoskin T, Boughey JC, Loprinzi C, Grant CS, Brandt KR, Pruthi S, Chute CG, Olson JE, Couch FJ, Ingle JN, Goetz MP. Trends in mastectomy rates at the Mayo Clinic Rochester: Effect of surgical year and preoperative magnetic resonance imaging. J Clin Oncol. 2009;27(25):4082-4088.
  4. McGuire KP, Santillan AA, Kaur P, Meade T, Parbhoo J, Mathias M, Shamehdi C, Davis M, Ramos D, Cox CE. Are mastectomies on the rise? A 13-year trend analysis of the selection of mastectomy versus breast conservation therapy in 5865 patients. Ann Surg Oncol. 2009;16(10):2682-2690.
  5. Wilson LD, Beinfield M, McKhann CF, Haffty BG. Conservative surgery and radiation in the treatment of synchronous ipsilateral breast cancers. Cancer.1993;72(1):137-142.
  6. Kurtz JM, Jacquemier J, Amalric R, Brandone H, Ayme Y, Hans D, Bressac C, Spitalier JM. Breast-conserving therapy for macroscopically multiple cancers. Ann Surg. 1990;212(1):38-44.
  7. Leopold KA, Recht A, Schnitt SJ, Connolly JL, Rose MA, Silver B, Harris JR. Results of conservative surgery and radiation therapy for multiple synchronous cancers of one breast. Int J Radiat Oncol Biol Phys. 1989;16(1):11-16.
  8. Bauman LR, Barth J, Rosenkranz KM. Breast conservation in women with multifocal-multicentric breast cancer: Is it feasible? Ann Surg Oncol. 2010;17(3):325-329.
  9. Gentilini O, Botteri E, Rotmensz N, Da Lima L, Caliskan M, Garcia-Etienne CA, Sosnovskikh I, Intra M, Mazzarol G, Musmeci S, Veronesi P, Galimberti V, Luini A, Viale G, Goldhirsch A, Veronesi U. Conservative surgery in patients with multifocal/multicentric breast cancer. Breast Cancer Res Treat. 2009;113(3):577-583.
  10. Hartsell WF, Recine DC, Griem KL, Cobleigh MA, Witt TR, Murthy AK. Should multicentric disease be an absolute contraindication to the use of breast-conserving therapy? Int J Radiat Oncol Biol Phys. 1994;30(1):49-53.
  11. Fowble B, Yeh IT, Schultz DJ, Solin LJ, Rosato EF, Jardines L, Hoffman J, Eisenberg B, Weiss MC, Hanks G. The role of mastectomy in patients with stage I-II breast cancer presenting with gross multifocal or multicentric disease or diffuse microcalcifications. Int J Radiat Oncol Biol Phys. 1993;27(3):567-573.
  12. Lim W, Park EH, Choi SL, Seo JY, Kim HJ, Chang MA, Ku BK, Son B, Ahn SH. Breast conserving surgery for multifocal breast cancer. Ann Surg. 2009;249(1):87-90.

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