Reirradiation of the Breast: Is This an Option?

Breast-conservation therapy (BCT) is a well-characterized treatment for early-stage breast cancer that has been studied for decades. The risk of local recurrence following BCT for invasive breast cancer ranges from 8.8% to 14.3% at 20 years.[1,2] Treatment without radiation does not appear to decrease overall survival in randomized clinical trials,[1,2] but in a meta-analysis, cancer mortality was slightly increased.[3] All randomized clinical trials published to date have included whole-breast radiation, limiting options for reirradiation. For primary tumors meeting criteria, data already exist to forgo radiation therapy,[4] suggesting that a second breast-conserving operation without radiation may be acceptable for selected patients.[4]

Criteria for a second course of BCT for recurrent or new ipsilateral tumors have been loosely defined by location within the breast, disease-free interval, and histology. These variables serve as surrogate indicators of new disease, as most local recurrences occur in the same quadrant, with a similar histology, and within 5 years following completion of therapy. This is an important distinction as recurrence is an independent predictor for breast cancer mortality,[5] whereas a new primary tumor carries a prognosis based upon the stage of disease. The distinction may become more predictable as molecular fingerprinting will ultimately characterize these two entities. For most patients, this is an academic point of interest that does not impact therapeutic planning with completion mastectomy representing the standard of care after an initial course of BCT. To date, there have been no prospective randomized trials to evaluate the role of breast-conservation therapy for a second ipsilateral primary or resectable recurrence.

For motivated patients declining a completion mastectomy, various criteria have been proposed. These include a time interval greater than 3 years, absence of late radiation changes in the skin or breast tissue, an early T stage of the new lesion (less than 3-cm primary), and the absence of involved nodes in the new lesion.[6] The greatest limitation with this treatment approach is the prior history of radiation therapy. As we move into an era of more limited disease detected by screening, there will be a continued proliferation of partial-breast radiation techniques, enabling greater latitude for the treatment of new primaries and recurrent disease.

Managing Recurrence Is Critical

From a prognosis standpoint, a recurrence carries a greater impact than a second primary. In the National Surgical Adjuvant Breast Protocol B-06, ipsilateral breast recurrence was an independent predictor for distant disease.[5] The timing of this event also has an impact on the patient's prognosis, serving as an indicator of a recurrence vs a new primary tumor. Veronesi and colleagues determined that the risk of developing a distant failure was 6.6 times higher if an ipsilateral breast tumor recurrence occurred during the first year after the diagnosis of cancer as compared to after the third year.[7] Managing the recurrence also appears to be critical for the patient's outcome. Successful local control after salvage surgery is associated with an overall survival of 78% vs 21% for patients who do not achieve local control.[8] Achieving local control can be viewed as either an opportunity to impact overall survival and local control or local control alone, depending upon whether a recurrence represents a controllable variable (if resectable) or a predictor of distant disease. Until this has been clarified, a safe approach would dictate a completion mastectomy for patients presenting with a recurrence, unless enrolled in a clinical trial.

New Primaries Should Be Approached Cautiously

Recognizing that the majority of local recurrences occur within the initially treated quadrant, new primaries may be approached with breast conservation cautiously and preferably within the context of a prospective clinical trial. In addition to the criteria enumerated above, breast MRI should be strongly considered given the increased difficulty in assessing the extent of the new primary due to surgery and radiation therapy changes. Conceptually, a second course of breast-conservation therapy could be offered optimally with a second course of partial-breast radiation therapy. As Drs. Chadha, Trombetta, and colleagues have indicated in this report, "Managing a Small Recurrence in the Previously Irradiated Breast: Is There a Second Chance for Breast Conservation?", local recurrence following a second breast-conserving lumpectomy without radiation ranges between 19% and 50% in small studies.[9]. With a second course of radiation, the local recurrence rate varies between 5% and 27%.[9]

In addition to effective cancer control, the motivated patient needs to consider the cosmetic outcome of a second course of breast-conservation therapy. This endpoint is defined by the location and size of the second primary tumor and the size of the remaining breast. Although a second course of breast-conservation therapy may be feasible, it may be cosmetically advantageous to pursue a completion mastectomy with reconstruction.

Repeat sentinel node biopsy has been evaluated in several single-institution studies, showing the potential to impact more accurate staging and regional control. Although not studied in a prospective randomized fashion to date, systemic therapy should be considered following a breast recurrence. For new primary tumors, this should be determined by the patient's stage and performance status, raising the relevance of identifying a sentinel node. As noted, a local recurrence following breast-conservation therapy is an independent predictor of overall survival, indicating the need to consider systemic therapy.

The clinician's ability to offer a second course of breast-conservation therapy will continue to expand as imaging technology improves, primary tumors become smaller, and partial-breast radiation therapy becomes more commonly implemented. Our precision in distinguishing a recurrence from a second primary tumor will also become critical to create well-controlled prospective clinical trials to determine accurate outcomes with this treatment approach.

Financial Disclosure: The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References:

1. Fisher B, Anderson S, Bryant J, et al: Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 47:1233-1241, 2002.
2. Veronesi U, Cascinelli N, Mariani L, et al: Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 47:1227-1232, 2002.
3. Early Breast Cancer Trialists’ Collaborative Group: Favourable and unfavourable effects on long-term survival of radiotherapy for early breast cancer: An overview of the randomised trials. Lancet 355:1757-1770, 2000.
4. Hughes KS, Schnaper LA, Berry D, et al: Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 351:971–977, 2004.
5. Fisher B, Anderson S, Fisher ER, et al: Significance of ipsilateral breast tumour recurrence after lumpectomy. Lancet 338:327-331, 1991.
6. Bloomer WD, LaCombe MA: Breast cancer in the irradiated breast, in Winchester DJ, Winchester DP, Hudis CA, et al (eds): Breast Cancer, p 448. BC Decker, Hamilton, Ontario, Canada, 2006.
7. Veronesi U, Marubini E, Del Vecchio M, et al: Local recurrences and distant metastases after conservative breast cancer treatments: Partly independent events. J Natl Cancer Inst 87:19-27, 1995.
8. Dalberg K, Liedberg A, Johansson U, et al: Uncontrolled local disease after salvage treatment for ipsilateral breast tumour recurrence. Eur J Surg Oncol 29:143-154, 2003.
9. Chadha M, Trombetta M: Managing a small recurrence in the previously irradiated breast: Is there a second chance for breast conservation? Oncology (Williston Park) 23:933-940, 2009.