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Local Control of Breast Cancer: Issues and Answers
editorial George W. Sledge, Jr., MD Division of Hematology/Oncology Indiana University School of Medicine Indianapolis, IN
Local Control of Breast Cancer: Issues and Answers As a medical student in the mid-1970s, I once had the temerity to ask the chairman of surgery of my medical school whether something less than a mastectomy might be acceptable. The chairman, fixing me with an icy stare, delivered an unanswerable and devastating response: “Dr. _____ [one of the early pioneers of breast preservation, unknown to a newer generation] has 7 malpractice suits pending against him for local failures.” And that was that, at least for another few years. The recent publication of the 25-year follow-up of the National Surgical Adjuvant Breast and Bowel Project’s trial B041 is a good time to ponder the problem of local control in breast cancer. Local control has been thought of as something of a backwater region of breast cancer therapy, with the main issue (the value of breast conservation compared to mastectomy) having been determined long ago. But as with hormonal therapy, local therapy continues to surprise. The past decade has seen several local therapy innovations and several lingering questions. The major lingering question involves postmastectomy radiation. Do we need it for patients with 1-3 positive lymph nodes? A large Southwest Oncology Group trial was supposed to answer the question, but the slow accrual to this important trial suggests that surgeons and radiation oncologists have already made up their minds, even if their minds don’t agree. On the innovation side, we continue to try to do more with less. Sentinel lymph node dissection took the breast cancer field by storm in the past decade, becoming a de facto standard of care. Partial breast irradiation techniques, which had fallen by the wayside in the early 1980s, are now staging something of a comeback, driven by novel techniques. Both sentinel lymph node biopsy and (increasingly) partial breast irradiation represent examples of appealing but untested (in the phase III proof-of-concept sense) technology—the surgical and radiation therapy equivalents of
the medical oncologist’s tendency to accept new agents without compelling data. The lymph node continues to arouse the interest of surgeons. Why, in the clinical stage I setting, do we remove lymph nodes? As a treatment to prevent metastasis and death? Or as a marker for distant metastasis and the need for systemic therapy? Will the emergence of new techniques (genomic evaluation of the primary tumor, or improved molecular-level imaging of the nodes) obviate the need for removing anything other than the primary tumor? In contrast to the less-is-more philosophy, will widespread screening for BRCA1 and BRCA2 (and other emerging markers of risk) lead to a significant increase in prophylactic mastectomy rates? Or will we perform more early (segmental) surgeries based on ductal lavage results in the same highrisk patients? And what of the interaction of systemic and local therapies? Will the use of accelerated radiation programs alter the timing of systemic therapy? Conversely, will systemic therapy reach a point of efficacy where it might replace some forms of local therapy, at least in some limited subsets? Or (as with tamoxifen for ductal carcinoma in situ) will it improve local control? What is clear from the above is that local therapy of breast cancer continues to challenge and evolve. We have solved the problem of local control of breast cancer several times in the past century. No doubt we will solve it again, and again, until we get it right. 01.Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. New Eng J Med 2002; 347:567-575.
George W. Sledge, Jr., MD Editor-in-Chief
Clinical Breast Cancer December 2002 • 301
Local Control of Breast Cancer: Issues and Answers As a medical student in the mid-1970s, I once had the temerity to ask the chairman of surgery of my medical school whether something less than a mastectomy might be acceptable. The chairman, fixing me with an icy stare, delivered an unanswerable and devastating response: “Dr. _____ [one of the early pioneers of breast preservation, unknown to a newer generation] has 7 malpractice suits pending against him for local failures.” And that was that, at least for another few years. The recent publication of the 25-year follow-up of the National Surgical Adjuvant Breast and Bowel Project’s trial B041 is a good time to ponder the problem of local control in breast cancer. Local control has been thought of as something of a backwater region of breast cancer therapy, with the main issue (the value of breast conservation compared to mastectomy) having been determined long ago. But as with hormonal therapy, local therapy continues to surprise. The past decade has seen several local therapy innovations and several lingering questions. The major lingering question involves postmastectomy radiation. Do we need it for patients with 1-3 positive lymph nodes? A large Southwest Oncology Group trial was supposed to answer the question, but the slow accrual to this important trial suggests that surgeons and radiation oncologists have already made up their minds, even if their minds don’t agree. On the innovation side, we continue to try to do more with less. Sentinel lymph node dissection took the breast cancer field by storm in the past decade, becoming a de facto standard of care. Partial breast irradiation techniques, which had fallen by the wayside in the early 1980s, are now staging something of a comeback, driven by novel techniques. Both sentinel lymph node biopsy and (increasingly) partial breast irradiation represent examples of appealing but untested (in the phase III proof-of-concept sense) technology—the surgical and radiation therapy equivalents of
the medical oncologist’s tendency to accept new agents without compelling data. The lymph node continues to arouse the interest of surgeons. Why, in the clinical stage I setting, do we remove lymph nodes? As a treatment to prevent metastasis and death? Or as a marker for distant metastasis and the need for systemic therapy? Will the emergence of new techniques (genomic evaluation of the primary tumor, or improved molecular-level imaging of the nodes) obviate the need for removing anything other than the primary tumor? In contrast to the less-is-more philosophy, will widespread screening for BRCA1 and BRCA2 (and other emerging markers of risk) lead to a significant increase in prophylactic mastectomy rates? Or will we perform more early (segmental) surgeries based on ductal lavage results in the same highrisk patients? And what of the interaction of systemic and local therapies? Will the use of accelerated radiation programs alter the timing of systemic therapy? Conversely, will systemic therapy reach a point of efficacy where it might replace some forms of local therapy, at least in some limited subsets? Or (as with tamoxifen for ductal carcinoma in situ) will it improve local control? What is clear from the above is that local therapy of breast cancer continues to challenge and evolve. We have solved the problem of local control of breast cancer several times in the past century. No doubt we will solve it again, and again, until we get it right. 01.Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical mastectomy, total mastectomy, and total mastectomy followed by irradiation. New Eng J Med 2002; 347:567-575.
George W. Sledge, Jr., MD Editor-in-Chief
Clinical Breast Cancer December 2002 • 301