Hormone-blocking therapy

Hormone-blocking therapy is a daily oral treatment taken for five years. Tamoxifen has long been the standard of care in women with ER-positive breast cancers.2 Tamoxifen is a selective estrogen-receptor modulator that binds to circulating estrogen and prevents it from attaching at any site in the body, reducing the likelihood of new breast tumor growth by 50% over five years.2 Side effects of this treatment include, but are not limited to, vasomotor symptoms (hot flushes, night sweats), weight gain, deep venous thrombosis, depression, elevated (but reversible) liver function, and uterine cancer (<1% and almost exclusively in postmenopausal women).2

Aromatase inhibitors (AIs) are among the newest generation of hormone-blocking therapies. These drugs block the production of estrogen in such ancillary sites as fat cells and the adrenal glands.2 Anastrozole (Arimidex), letrozole (Femara), and exemestane (Aromasin) are the AIs currently approved by the FDA and recommended by the NCCN guidelines.10 Because AIs have not been extensively tested in the premenopausal setting, they are only approved for postmenopausal patients, although clinical trials are ongoing.2


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Initial trial results indicate that anastrozole is superior to tamoxifen in terms of increasing disease-free survival and time to recurrence and decreasing the risk of contralateral breast cancer in postmenopausal women.12 The side-effect profile of AIs is fairly minimal in comparison with tamoxifen but does include accelerating osteoporosis, elevation of cholesterol level, arthralgias, weight gain, and nausea.2

Chemotherapy is the recommendation in a patient with Stage I breast cancer with a high histologic grade, tumor size >1 cm, and/or a high recurrence score on the Oncotype DX. Trastuzumab will be offered if the HER2/neu status is reported as overexpressed (3+ by FISH). Hormone-blocking therapy will be offered if the tumor is estrogen-receptor positive.

Discussion

Breast cancer treatment involves a systematic and incredibly complex decision-making process. Extensive research has been dedicated to each and every facet of diagnosing and treating this disease.

Treatment of Stage I disease is difficult and requires a complete dissection and understanding of the pathology. BCT has a clear advantage for women wishing to save their breasts. Mastectomy is recommended in patients who prefer not to undergo radiation therapy.

Whether to treat early-stage breast cancer with adjuvant chemotherapy is the more difficult question to answer, as most patients will receive minimal benefit compared with the potential risk of side effects associated with chemotherapy. Hormone-blocking therapy provides the greatest reduction in risk of recurrence in patients with early-stage, ER-positive, node-negative breast cancer. Chemotherapy is known to provide little benefit in terms of overall survival in this stage. However, with the advent of new and improved technology and testing, identifying those patients who will benefit from chemotherapy assists in the decision-making process and can help avoid potential toxic side effects from unnecessary treatment in the low-RS individuals.13 Stage I breast tumors with a higher RS are more likely to respond to chemotherapy than those with a low or intermediate RS.11

Treatment of patients with an intermediate RS remains a gray area. Current clinical trials will help sort this group into a more definitive treatment category: chemotherapy benefit or no chemotherapy benefit.13 In the meantime, when the RS falls in the 11-25 range, treatment options include chemotherapy followed by hormone-blocking therapy.

The decision ultimately belongs to the patient. However, providing as much pertinent information as possible, including results from both past and current clinical trials, will lead to an informed decision regarding the patient’s care and overall survival.

Ms. Kentley is a physician assistant at Medical Oncology Group Health Cooperative in Tacoma, Wash. She has no relationships to disclose relating to the content of this article.

References

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2. OE Silva and S Zurrida, eds. Breast Cancer: A Practical Guide, 3rd ed., Philadelphia, Pa.: Elsevier Saunders; 2005.

3. Litherland JC, Evans AJ, Wilson AR, et al. The impact of core-biopsy on pre-operative diagnosis rate of screen detected breast cancers. Clin Radiol. 1996;51:562-565.

4. Li CI, Uribe DJ, Daling JR. Clinical characteristics of different histologic types of breast cancer. Br J Cancer. 2005;93:1046-1052.

5. Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11:155-168.

6. Harris L, Fritsche H, Mennel R, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287-5312.

7. van Dongen JA, Voogd AC, Fentiman IS, et al. Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst. 2000;92:1143-1150.

8. 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. 2002;347:1233-1241. 

9. Giuliano AE, Hunt KK, Ballman KV, et al. Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA. 2011;305:569-575.

10. Bevers TB, Anderson BO, Bonaccio E, et al. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis. J Natl Compr Canc Netw. 2009;7:1060-1096.

11. Paik S, Tang G, Shak S, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol. 2006;24:3726-3734. 

12. Baum M, Buzdar A, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer. 2003;98:1802-1810.

13. ClinicalTrials.gov. Hormone Therapy With or Without Combination Chemotherapy in Treating Women Who Have Undergone Surgery for Node-Negative Breast Cancer (The TAILORx Trial).

All electronic documents accessed March 15, 2011.