Edited comments by Seema A Khan, MD

CALGB-9343: Whole breast irradiation versus no further therapy in elderly women

CALGB-9343 recruited women 70 years of age or older with tumors no greater than two centimeters and negative margins. The patients underwent breast-conserving surgery, received adjuvant tamoxifen and were randomly assigned to receive radiotherapy or not. The major endpoint was local recurrence and now, with at least four years of follow-up, the rate is one percent in the radiated group and four percent in the patients who did not undergo radiation. As this study demonstrates, women age 70 and older have a very low recurrence risk to begin with, so the value of radiation for smaller tumors may be questionable. In these patients, when radiation is utilized, partial breast irradiation might be useful, but we have limited data to suggest cosmesis is equivalent to standard radiation therapy.

Assessment of ER status in patients with DCIS

In the original NSABP-B-24 study, which randomly assigned women with DCIS to adjuvant tamoxifen versus placebo, ER status was not measured. Craig Allred and the NSABP subsequently retrieved 600 to 800 blocks from that trial and found that ER status strongly influenced the benefit from tamoxifen, whereas in patients with ER-negative disease, the recurrence rates were almost identical and the small, nonsignificant benefit seen was probably related to quality control of the ER assay. Quality control in determining estrogen status is an important issue. Grade I DCIS is almost always positive; if it's reported as ER-negative, one should question the accuracy of the assay.

Adjuvant endocrine therapy and the surgeon's role

It is rare for women to discontinue adjuvant tamoxifen due to toxicities and in our experience, adherence to tamoxifen therapy is excellent. We have also found patients very tolerant of the aromatase inhibitor side effects. I've seen slightly more of the musculoskeletal side effects than I expected, particularly arthralgias. A few patients have discontinued anastrozole, but in most patients it's extremely well tolerated.

We utilize alendronate more in women receiving anastrozole than in women receiving tamoxifen, but anastrozole's increased efficacy and better tolerability makes it worthwhile to use the aromatase inhibitor. Examining the data from the ATAC trial, the efficacy curves are separating, so there probably is an advantage to anastrozole. Of course, each patient's comorbidities need to be considered. For example, in a frail patient with a history of osteoporosis, the small improvement in efficacy associated with anastrozole may be offset by its effects on bone mineral density.

As the palate of endocrine therapy increases in complexity, probably more surgeons will defer to medical oncologists rather than prescribe adjuvant endocrine therapy. I've started many women on tamoxifen in my surgical career, fewer on aromatase inhibitors, but in general I encourage women to discuss adjuvant endocrine therapy with a medical oncologist. I discuss adjuvant therapy with them as well, but I believe it's helpful for patients to have two perspectives on this issue. The level of comfort each surgeon has with these discussions varies, as does the amount of information they will provide and how much they'll participate in the decision making.

Resection of the primary in women with de novo metastatic disease

SWOG published data from a study of Stage IV renal cell carcinoma in which patients with intact primary tumors were randomly assigned to systemic therapy with or without resection of the primary tumor. A statistically significant median increase in survival of approximately three months was seen in patients who underwent resection. Prompted by this data, we examined the National Cancer Data Base (NCDB) for the utilization of resection of the primary tumor in women with de novo metastatic breast cancer and whether resection impacted survival (Figures 1.1, 1.2).

We found that 60 percent of women who present with metastatic breast cancer and intact primary tumors are resected, and those women have a better survival rate. In addition, a clear margin status had a significant impact on survival, extending the three-year mean from approximately 19 months in patients who did not have their primary tumor resected, to 32 months in patients receiving a total mastectomy. Chest wall disease is a major concern for patients and physicians alike, which is one of the reasons these patients undergo resection of the primary tumor. However, we currently don't have good data on how often uncontrolled chest wall disease occurs.

The SWOG trial offers the first suggestive evidence from a large data set that there may be an advantage to resection of the primary tumor with metastases present. In the absence of randomized trial data, individual practitioners are left with the decision of how to manage these cases. I see a handful of these cases each year and, in consultation with the medical oncologist, we begin with systemic therapy. If the woman responds well to systemic therapy and is relatively free of co-morbidities, then I discuss resection of the primary tumor with her.

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