Updated: November 2004
The management of LABC requires a combined modality treatment approach involving surgery, radiation and systemic therapy. Although patients with stage IIIA (T3 N1) disease are potentially operable, primary (pre-op) systemic chemotherapy or adjuvant chemotherapy following surgery have equivalent survival outcomes and either approach can be used.
Patients with inoperable stage IIIB (any T4,any N2) disease, including inflammatory breast cancer and those with stage IIIC (isolated ipsilateral internal mammary or supraclavicular lymph node involvement i.e. N3) should be treated with primary anthracycline-based chemotherapy first [1].
Chemotherapy
The function of the chemotherapy is both to attempt to eradicate micrometastases, to improve the loco-regional control and to render the patient operable. For women < 60 years of age, acceptable treatment options include CEF
or AC followed by docetaxel. Two clinical trials suggest an improvement in pCR for docetaxel based regimens, but this has not been shown to have an effect on survival. The BCCA currently has two clinical trials open for patients with LABC and referral to a BCCA medical oncologist for participation should be considered.[2, 3] Women over 60 years of age should be treated with CAFpo or AC followed by docetaxel. There are no studies to compare the efficacy of these two regimens. AC-Taxol has not been reported on in this situation, although there may be efficacy in ER negative disease. Responding patients should receive a total of 6-8 cycles of treatment, depending on which regimen is used.
If no significant tumour response is seen after 2-3 cycles of anthracyline based chemotherapy then a taxane can be used or the patient can proceed directly to loco-regional irradiation.
Loco-regional Therapy
Patients who are rendered operable following chemotherapy can proceed directly to modified radical mastectomy or loco-regional irradiation. Breast conserving surgery is currently not a standard approach. When both surgery and radiation are employed loco-regional control is improved. However, there is no good data to support which scheduling of radiation and surgery is most effective. Outside a clinical trial the standard order of treatment for locally advanced disease should be chemotherapy, followed by irradiation and then followed by surgery, unless there are individual patient reasons to change the order. Clinical trials with an endpoint of surgical response following chemotherapy may prescribe the surgery prior to the irradiation. In cases where immediate reconstruction is being performed irradiation should be given before the surgery outside of a clinical trial. In all cases the patient should be assessed for operability after response to therapy and a metastatic work-up repeated, prior to proceeding with a modified radical mastectomy.
Hormone Therapy
Tamoxifen 20 mg po daily for 5 years is offered to all patients with estrogen or progesterone positive LABC. Anastrozole is an alternative option as primary adjuvant therapy but is currently under review for funding in B.C. for this indication[4]. Letrozole 2.5 mg po daily should be considered for all postmenopausal women who remain disease free following 5 years of Tamoxifen.[5]
Patients with estrogen or progesterone positive LABC who are unsuitable for chemotherapy may be treated with primary systemic hormone therapy, usually letrozole, and locoregional irradiation.
Treatment Following Neoadjuvant Chemotherapy, Radiation and Surgery
There is not data at this time to suggest that additional chemotherapy is of benefit in patients who have received the full neoadjuvant prescription and have residual disease at surgery.
References:
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Shenkier, T., et al., Clinical practice guidelines for the care and treatment of breast cancer: 15. Treatment for women with stage III or locally advanced breast cancer. CMAJ, 2004. 170(6): p. 983-994.
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Smith, I.C., et al., Neoadjuvant Chemotherapy in Breast Cancer: Significantly Enhanced Response With Docetaxel. J Clin Oncol, 2002. 20(6): p. 1456-1466.
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Therasse, P., et al., Final Results of a Randomized Phase III Trial Comparing Cyclophosphamide, Epirubicin, and Fluorouracil With a Dose-Intensified Epirubicin and Cyclophosphamide + Filgrastim as Neoadjuvant Treatment in Locally Advanced Breast Cancer: An EORTC-NCIC-SAKK Multicenter Study. J Clin Oncol, 2003. 21(5): p. 843-850.
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Group, T.A.T., Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial.[comment]. Lancet., 2002. 359(9324): p. 2131-9.
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Goss, P.E., et al., A Randomized Trial of Letrozole in Postmenopausal Women after Five Years of Tamoxifen Therapy for Early-Stage Breast Cancer. N Engl J Med, 2003. 349(19): p. 1793-1802.