Conferences > OncoLink Scientific Meetings Coverage > OncoLink at the San Antonio Breast Cancer Symposium 2006 > Highlights from SABCS 2006

OncoLink Professor On-Call: Lawrence Solin, MD provides exclusive expert review and insights from the recent San Antonio Breast Cancer Symposia for OncoLink

Lawrence J. Solin, M.D., F.A.C.R.
The Abramson Cancer Center of the University of Pennsylvania
Posting Date: December 16, 2006

The 29th Annual San Antonio Breast Cancer Symposium was held from Thursday, December 14 through Sunday, December 17, 2006. A wide range of topics was discussed. This symposium is widely considered to be one of the major breast cancer conferences in the world. As such, much of the scientific information presented at this symposium is quickly integrated into contemporary breast cancer practice.

Epidemiology and Prevention

Dr. Peter Ravdin presented data from SEER (Surveillance, Epidemiology, and End Results) that showed a dramatic and statistically significant decrease in the incidence of breast cancer in the United States between 1998 and 2003. The absolute decrease in the number of new breast cancer cases was about 14,000 in 2003. Given that the SEER data represent a cross-section of the United States, these results are an important public health finding. The authors hypothesized that the decline in the widespread use of hormone replacement therapy (HRT) may account for these findings. If correct, these results could have large-scale public health implications, and suggest that public health measures can have a dramatic and meaningful impact on overall health relative to a specific disease outcome.

The WINS (Women's Intervention Nutrition Study) randomized 2,437 patients to reduced fat intake compared to control. In addition to reduced fat intake, mean body weight was also significantly lower in the intervention group (p = .005). The hazard ratio for the intervention group was .76 for breast cancer events. These results suggest that dietary interventions can significantly reduce the risk of breast cancer, which of course has enormous public health implications. Subset analysis suggested that the effect was mainly for the patients with hormone receptor negative tumors, a group for which hormone treatments are ineffective. The mechanism of the improved outcome is unclear, but is hypothesized to occur through nonhormonal pathways. The improvement in outcome for the intervention group might relate to the reduction in dietary fat intake, lower body weight, or both. First results from this study are scheduled for publication shortly (Chlebowski R, JNCI, in press).

Updated results were presented from the NSABP (National Surgical Adjuvant Breast and Bowel Project) STAR (study of tamoxifen and raloxifene) P-2 trial. In this study, 19,747 postmenopausal women at increased risk for developing breast cancer were randomized to receive 5 years of tamoxifen vs. raloxifene. In a prior report, no differences were reported between the two groups for the development of invasive breast carcinoma, although tamoxifen was reported to have a lower rate of development of non-invasive breast carcinoma. The toxicity profiles for the two agents were both acceptably low, but slightly different. In the updated results, the tamoxifen arm continues have lower rates of developing DCIS (risk ratio = 1.46), LCIS (risk ratio = 1.37), and all non-invasive events (risk ratio = 1.40). The mechanism for this differential effect remains uncertain, but suggests that the mechanism by which chemoprevention works is complex.

In clinical practice, these updated results confirm the initial findings of a differential effect between tamoxifen and raloxifene, and suggest that while either agent is effective for the primary endpoint of reduction for invasive carcinoma, the choice of agent for the individual patient might be influenced by the subtle differences in the toxicity profile. Further, if an individual patient does not tolerate one of the two agents, changing to the other can be considered.

In a discussion of breast cancer prevention, Dr. Leslie Ford from the National Cancer Institute suggested guidelines for selecting a chemoprevention agent. For the premenopausal woman, tamoxifen is the only agent with demonstrated effectiveness. In the postmenopausal setting, raloxifene is preferred for the woman with a uterus (because of the lower risk of endometrial cancer associated with raloxifene compared to tamoxifen), and either tamoxifen or raloxifene can be considered for the woman without a uterus. Future trials will evaluate the potential efficacy of an aromatase inhibitor for prevention in the postmenopausal woman.

Early Stage Disease: Local-Regional Treatment

The first report from the ECOG (Eastern Cooperative Oncology Group) E5194 study was presented. In this study, carefully selected patients with low risk DCIS were prospectively identified for treatment with excision alone, without breast radiation. Adjuvant tamoxifen was optional. Low risk patients in this study were defined as: (a) low-intermediate grade plus size < 2.5 cm or high grade plus size < 1.0 cm; (b) excision of the primary DCIS lesion; (c) pathologically confirmed negative margins with a minimum negative margin width of 3 mm or no tumor in a re-excision specimen; and (d) post biopsy mammogram with no residual microcalcifications for those lesions presenting initially with microcalcifications on mammography. All specimens underwent rigorous pathologic evaluation with serial sectioning.

The results from this study demonstrated a relatively low risk of local recurrence of 6.8% at 5 years for the low-intermediate DCIS subset. However, the risk of local recurrence was 13.7% at 5 years for the high grade subset.

The importance of this study is that it is one of the first large studies to attempt to identify prospectively patients who can be treated with omission of radiation, albeit with careful patient selection and rigorous evaluation of the pathologic specimen. Before these results are implemented in routine clinical practice, caveats regarding the interpretation of this data include the relatively short follow-up (median 5 years) and limited information about clinically important subsets (e.g., use of tamoxifen, patient age, minimum negative margin width). In clinical practice, these results demonstrate that high grade lesions cannot adequately be treated with excision alone, and that radiation should be included as a component of management. Relative to low-intermediate grade lesions, the outcomes will need to be strengthened with longer follow-up, and subset information will be useful to better tailor treatment for these lesions.

Dr. Harry Bartelink presented an update of the EORTC (European Organization for Research and Treatment of Cancer) trial 22881-10882. After breast conserving surgery, pathologically confirmed negative margins, and whole breast radiation of 50 Gy, patients in this study were randomized to receive an additional 16 Gy radiation boost to the primary tumor site compared to no boost. The results showed an improvement in local recurrence for the overall group with an absolute benefit of 4.0% at 10 years (6.2% vs. 10.2%; p < .0001). Further, all age subsets showed an improvement in local recurrence ranging from an absolute benefit of 10.4% at 10 years for patients age < 40 years (p = .0014) to 3.5% for patients age > 60 years (p .0008). There were fewer distant failures in the radiation boost group (305 vs. 353, respectively), but this has not yet translated into a difference in survival at 10 years (82% in both groups; p = .93). The use of a radiation boost was associated with a slightly increased risk of fibrosis of 2.8% (p < .0001).

In clinical practice, this EORTC study strongly suggests that all breast conservation patients, regardless of age, should receive a radiation boost to the primary tumor site after conventional whole breast radiation. Most radiation oncologists routinely add a boost after whole breast radiation. Although the early results from this study were not as strongly in favor of the boost for the older age group, the updated results from this study indicate that all patients benefit from the addition of the radiation boost. The boost treatment resulted in a small, but acceptably, increased rate of fibrosis after treatment. Although this trial showed a dose response effect in favor of higher radiation doses, it is unlikely that even higher radiation doses (beyond 65-66 Gy) will be tested in randomized trials because of the known risks of substantially increased complications with these higher doses, as well as the excellent local control rates seen with conventional radiation doses. On balance, total radiation doses in the range of 60-66 Gy appear to be the optimal range for breast conservation treatment to balance the high rate of local control with a low risk of complications.

The optimal management of older women continues to be actively investigated. In a randomized trial, 636 women with estrogen receptor positive, T1 tumors received lumpectomy and tamoxifen, and were then randomly assigned to radiation vs. no radiation. With a median follow-up of 7.9 years, the absolute benefit for local-regional recurrence was about 6% better for the radiation arm (7% vs.1%; p = .0001), and improvements in both local control and regional control were demonstrated. This study demonstrated its primary endpoint of an improvement in local control associated with radiation treatment. The study was not sufficiently powered to detect differences in survival or distant metastases, and the results of these endpoints of study are accordingly not different.

The clinical importance of this study must be put into the context of the performance status of the individual patient. An otherwise healthy 70-year old woman has an estimated life expectancy of approximately 19 years, and an otherwise healthy 80-year old woman has an estimated life expectancy of approximately 9 years. In the older age category, breast cancer treatment should consider the disease in the context of the patient. For example, a healthy 70-year old woman without significant co-morbidities deserves maximally aggressive treatment (including surgery, adjuvant systemic treatment, and conventional radiation), whereas an 85-year old woman with substantial co-morbidities might reasonably be treated with a less aggressive program (e.g., lumpectomy plus adjuvant hormonal therapy).

Dr. Bruno Cutuli presented intriguing data on a retrospective cohort of 325 patients with LCIS (lobular carcinoma in situ) of the breast. The majority (77%) of the patients underwent “conservative surgery,” although the meaning of this term is uncertain in the context of LCIS. After conservative surgery, the 10-year rate of local recurrence was 23%, of which 55% were invasive. The 10-year rate of contralateral breast cancer was 7.8%, of which 70% were invasive. Radiation after conservative surgery was associated with a decrease in local recurrence compared to no radiation (5.4% vs. 19.2%, respectively). Given the ipsilateral and contralateral risks associated with LCIS, the clinical importance of this diagnosis is to identify these patients with LCIS as high risk and potential candidates for prevention strategies. While prophylactic mastectomy is curative, prevention strategies are typically chosen by patients in lieu of more radical surgery.