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Lumpectomy Plus Tamoxifen or Arimidex With or Without Whole Breast Irradiation in Women with Favorable Early Breast Cancer

Reviewer: Thomas Dilling, MD
Abramson Cancer Center of the University of Pennsylvania
Ultima Vez Modificado: 17 de octubre del 2005

Presenter: R. Poetter
Presenter's Affiliation: Dept. of Radiotherapy and Radiobiology, Medical University of Vienna
Type of Session: Plenary

Background
In treating early-stage breast cancers with favorable prognostic features, the question has been raised as to whether oncologists might be overtreating these patients. In other words, is it necessary to treat an elderly patient with as aggressive a treatment regimen as a younger patient?

The recent CALGB 9343 trial looked at patients with age >70 years, ER+ T1 tumors, who had lumpectomy with negative margins. These patients were treated with either radiation/tamoxifen or tamoxifen alone. With 7 year median follow-up, disease-free survival (DFS) was statistically greater in the patients treated with radiation (99%) vs those treated with tamoxifen alone (94.4%), with equivalent rates of breast preservation in patients who did recur.

This trial, conducted independently by the Austrian Breast and Colorectal Cancer Group looked at a similar question, as addressed by this study.

Materials and Methods

• Patients enrolled were postmenopausal, with tumors < 3cm in size which were ER+ and/or PR+, surgically managed with lumpectomy, with pathologically negative margins. Tumors were grade I or II only.  All patients had surgical management of the axilla, defined in the early years of the study as axillary dissection (>10 LNs removed), or, in the later years, with sentinel lymph node biopsy. All patients were N0.
• All patients were treated with arimidex or tamoxifen.
• 410 patients received radiation therapy (50 Gy +/- 10 Gy boost via electron therapy or brachytherapy). 66% of patients received the boost. Average dose to the whole breast for patients not receiving a boost was 51 Gy.
• 416 patients were assigned to the "no radiotherapy" arm.
• Primary endpoint was local recurrence (LR). Other endpoints included contralateral breast cancer occurence, rate of distant metastasis (DM), disease-free survival (DFS), and overall survival (OS).
• Patients were stratified by age, tumor size, tumor grade, and cancer treatment center in an intent-to-treat analysis.
• Patients accrued from 1/96 to 6/04. Median follow-up to date is 43 months.

Results

• Patients were well-balanced in the two treatment groups.
• Mean patient age was 66 years.
• To date, there have been 14 local recurrences, with one occurring in a patient receiving XRT(0.2% LR) , vs 13 who did not receive XRT (3.1% LR) (p=0.0001).
• No contralateral breast cancers have occurred in patients who received radiotherapy, vs 4 who did not (p=0.04).
• Rate of distant metastasis is eqivalent between the two arms, with 5 and 4 patients, respectively.
• Overall survival is equivalent in the two arms (97.8% vs 96.6%, respectively), with a non-significant p-value.

Author's Conclusions

• The authors emphasize that there is a statistically-significant increase in local recurrence in the patients who did not recieve XRT, but local control is excellent in both groups.
• This has failed to translate into a difference in OS. 
• Radiation therapy remains the standard of care for postoperative treatment of patients with early stage breast cancer to decrease the risk of local failure.
  

Clinical/Scientific Implications

The  follow-up on this study is still relatively short and further analysis will be necessary in the future. Nonetheless, it is an interesting confirmatory study of the  results from the CALGB trial.   The rates of local control in this population with early stage cancer are excellent overall to date.  The addition of radiation therapy clearly reduces the rate of local recurrence. 

A difficulty which oncologists still face is in deciding which patients would benefit from radiotherapy. If a patient with a T1N0, favorable-prognosis tumor is otherwise quite elderly and debilitated, it would be reasonable to consider omitting radiotherapy for treatment with hormonal therapy only as the local control is excellent. However, while age is a convenient metric to use when treating patients, it is nonetheless vital to remember that not all patients of the same age have the same life expectancy. If a patient is expected to live for a number of years to come, based upon overall good health and performance status, it would make more sense to treat the patient with XRT to further reduce the chances of local recurrence. But there remains a group of patients who are "in between" these extremes. This requires a difficult clinical judgment on the part of the treating oncologists, which needs to be discussed with the patient. Individualized treatment is clearly of vital importance in treating the elderly patient with favorable, early-stage breast cancer.