Breast Cancer Treatment (Adult) (PDQ®)–Health Professional Version

Locally Advanced or Inflammatory Breast Cancer

Treatment Option Overview for Locally Advanced or Inflammatory Breast Cancer

On the basis of the available evidence, multimodality therapy delivered with curative intent is the standard of care for patients with locally advanced or inflammatory breast cancer.

The standard treatment options for locally advanced or inflammatory breast cancer may include the following:

Breast-conserving surgery or total mastectomy with axillary lymph node dissection.
Chemotherapy.
Radiation therapy.
Hormone therapy.

Initial surgery is generally limited to biopsy to permit the determination of histology, estrogen receptor (ER) and progesterone receptor levels, and human epidermal growth factor receptor 2 (HER2/neu) overexpression.

The standard chemotherapy regimen for initial treatment is the same as that used in the adjuvant setting (refer to the Postoperative Systemic Therapy section of this summary for more information), although trials done solely in patients with locally advanced disease have not shown a statistically significant advantage to dose-dense chemotherapy.[1]

For patients who respond to preoperative chemotherapy, local therapy may consist of total mastectomy with axillary lymph node dissection followed by postoperative radiation therapy to the chest wall and regional lymphatics. Breast-conserving therapy can be considered for patients with a good partial or complete response to preoperative chemotherapy.[2] Subsequent systemic therapy may consist of further chemotherapy. Hormone therapy is administered to patients with ER-positive or ER-unknown tumors.

Although the evidence described below has not been replicated, it suggests patients with locally advanced or inflammatory breast cancer should be treated with curative intent.

Evidence (multimodality therapy):

In a retrospective series, 70 patients with locally advanced breast cancer and supraclavicular metastases received preoperative chemotherapy. Patients then received local therapy that consisted of either total mastectomy and axillary lymph node dissection or breast-conserving surgery and axillary lymph node dissection before or after radiation therapy. Patients who did not respond to preoperative chemotherapy were treated with surgery and/or radiation therapy. After completion of local therapy, chemotherapy was continued for 4 to 15 cycles, followed by radiation therapy.[3]
- Approximately 32% of patients with ipsilateral supraclavicular node involvement and no evidence of distant metastases (pN3c) had prolonged disease-free survival (DFS) at 10 years with combined-modality therapy.
- These results have been confirmed in a separate series of patients treated in British Columbia.[4]
A series of 178 patients with inflammatory breast cancer were treated with a combined-modality approach. Patients were treated with induction chemotherapy, then local therapy (radiation therapy or mastectomy), followed by chemotherapy, and, if mastectomy was performed, radiation therapy.[5][Level of evidence: 3iiiDii]

Subsequent trials have confirmed that patients with locally advanced and inflammatory breast cancer can experience long-term DFS when treated with initial chemotherapy.[1]

All patients are considered candidates for clinical trials to evaluate the most appropriate way to administer the various components of new multimodality regimens.

Current Clinical Trials

Use our advanced clinical trial search to find NCI-supported cancer clinical trials that are now enrolling patients. The search can be narrowed by location of the trial, type of treatment, name of the drug, and other criteria. General information about clinical trials is also available.

References

Petrelli F, Coinu A, Lonati V, et al.: Neoadjuvant dose-dense chemotherapy for locally advanced breast cancer: a meta-analysis of published studies. Anticancer Drugs 27 (7): 702-8, 2016. [PUBMED Abstract]
Berg CD, Swain SM: Results of Concomitantly Administered Chemoradiation for Locally Advanced Noninflammatory Breast Cancer. Semin Radiat Oncol 4 (4): 226-235, 1994. [PUBMED Abstract]
Brito RA, Valero V, Buzdar AU, et al.: Long-term results of combined-modality therapy for locally advanced breast cancer with ipsilateral supraclavicular metastases: The University of Texas M.D. Anderson Cancer Center experience. J Clin Oncol 19 (3): 628-33, 2001. [PUBMED Abstract]
Olivotto IA, Chua B, Allan SJ, et al.: Long-term survival of patients with supraclavicular metastases at diagnosis of breast cancer. J Clin Oncol 21 (5): 851-4, 2003. [PUBMED Abstract]
Ueno NT, Buzdar AU, Singletary SE, et al.: Combined-modality treatment of inflammatory breast carcinoma: twenty years of experience at M. D. Anderson Cancer Center. Cancer Chemother Pharmacol 40 (4): 321-9, 1997. [PUBMED Abstract]

Locoregional Recurrent Breast Cancer

Recurrent breast cancer is often responsive to therapy, although treatment is rarely curative at this stage of disease. Patients with locoregional breast cancer recurrence may become long-term survivors with appropriate therapy.

The rates of locoregional recurrence have been reduced over time, and a meta-analysis suggests a recurrence rate of less than 3% in patients treated with breast-conserving surgery and radiation therapy.[1] The rates are somewhat higher (up to 10%) for those treated with mastectomy.[2] Nine percent to 25% of patients with locoregional recurrence will have distant metastases or locally extensive disease at the time of recurrence.[3-5]

Before treatment for recurrent breast cancer, restaging to evaluate the extent of disease is indicated. Cytologic or histologic documentation of recurrent disease is obtained whenever possible. When therapy is selected, the estrogen-receptor (ER) status, progesterone-receptor (PR) status, and human epidermal growth factor receptor 2 (HER2/neu) status at the time of recurrence and previous treatment are considered, if known.

ER status may change at the time of recurrence. In a single small study by the Cancer and Leukemia Group B (MDA-MBDT-8081), 36% of hormone receptor–positive tumors were found to be receptor negative in biopsy specimens isolated at the time of recurrence.[6] Patients in this study had no interval treatment. If ER and PR statuses are unknown, then the site(s) of recurrence, disease-free interval, response to previous treatment, and menopausal status are useful in the selection of chemotherapy or hormone therapy.[7]

Treatment options for locoregional recurrent breast cancer include the following:

Chemotherapy.
Hormone therapy.
Radiation therapy.
Surgery.
Targeted therapy (e.g., trastuzumab).

Patients with locoregional recurrence should be considered for further local treatment (e.g., mastectomy). In one series, the 5-year actuarial rate of relapse for patients treated for invasive recurrence after initial breast conservation and radiation therapy was 52%.[4]

Treatment options also depend on the site of recurrence, as follows:

Cutaneous: A phase III randomized study showed that local control of cutaneous metastases could be achieved with the application of topical miltefosine; however, the drug is not currently available in the United States.[8][Level of evidence: 1iiDiii]
Chest wall: Local chest wall recurrence after mastectomy is usually the harbinger of widespread disease, but, in a subset of patients, it may be the only site of recurrence. For patients in this subset, surgery and/or radiation therapy may be curative.[9,10] Patients with chest wall recurrences of less than 3 cm, axillary and internal mammary node recurrence (not supraclavicular, which has a poorer survival), and a greater-than-2-year disease-free interval before recurrence have the best chance for prolonged survival.[10] The 5-year disease-free survival (DFS) rate in one series of such patients was 25%, with a 10-year rate of 15%.[11] The locoregional control rate was 57% at 10 years. Systemic therapy should be considered in patients with locoregional recurrence.
Breast: In the Chemotherapy as Adjuvant for Locally Recurrent Breast Cancer (CALOR [NCT00074152]) trial, patients with a history of breast-conserving surgery or mastectomy with clear margins and complete excision of an isolated local recurrence of their breast cancer were randomly assigned to receive either chemotherapy of the physician's choice or no chemotherapy. The study was closed early because of poor accrual. The original sample size for a hazard ratio (HR) of 0.74 was 977 patients (347 DFS events) and was revised subsequently to 265 patients (HR 0.6; 124 DFS events), with only 162 enrolled at the time of study closure.[12][Level of evidence: 1iiDii]
- In ER-negative patients, the HR for DFS for chemotherapy versus no chemotherapy was 0.29 (95% CI, 0.13–0.67; 10 years DFS, 70% vs. 34%), whereas in ER-positive patients, the HR was 1.07 (95% CI, 0.57–2.00; 10 years DFS, 50% vs. 59%). The interaction between chemotherapy and ER status with respect to DFS was significant (P = .013).[13]
- This trial supports consideration of adjuvant chemotherapy after complete resection of isolated locoregional recurrence of breast cancer in patients with ER-negative tumors.

(Refer to the Metastatic (systemic) disease section of this summary for information about treatment for recurrent metastatic breast cancer.) All patients with recurrent breast cancer are considered candidates for ongoing clinical trials.

Current Clinical Trials

References

Darby S, McGale P, Correa C, et al.: Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet 378 (9804): 1707-16, 2011. [PUBMED Abstract]
Buchanan CL, Dorn PL, Fey J, et al.: Locoregional recurrence after mastectomy: incidence and outcomes. J Am Coll Surg 203 (4): 469-74, 2006. [PUBMED Abstract]
Aberizk WJ, Silver B, Henderson IC, et al.: The use of radiotherapy for treatment of isolated locoregional recurrence of breast carcinoma after mastectomy. Cancer 58 (6): 1214-8, 1986. [PUBMED Abstract]
Abner AL, Recht A, Eberlein T, et al.: Prognosis following salvage mastectomy for recurrence in the breast after conservative surgery and radiation therapy for early-stage breast cancer. J Clin Oncol 11 (1): 44-8, 1993. [PUBMED Abstract]
Haffty BG, Fischer D, Beinfield M, et al.: Prognosis following local recurrence in the conservatively treated breast cancer patient. Int J Radiat Oncol Biol Phys 21 (2): 293-8, 1991. [PUBMED Abstract]
Kuukasjärvi T, Kononen J, Helin H, et al.: Loss of estrogen receptor in recurrent breast cancer is associated with poor response to endocrine therapy. J Clin Oncol 14 (9): 2584-9, 1996. [PUBMED Abstract]
Perry MC, Kardinal CG, Korzun AH, et al.: Chemohormonal therapy in advanced carcinoma of the breast: Cancer and Leukemia Group B protocol 8081. J Clin Oncol 5 (10): 1534-45, 1987. [PUBMED Abstract]
Leonard R, Hardy J, van Tienhoven G, et al.: Randomized, double-blind, placebo-controlled, multicenter trial of 6% miltefosine solution, a topical chemotherapy in cutaneous metastases from breast cancer. J Clin Oncol 19 (21): 4150-9, 2001. [PUBMED Abstract]
Schwaibold F, Fowble BL, Solin LJ, et al.: The results of radiation therapy for isolated local regional recurrence after mastectomy. Int J Radiat Oncol Biol Phys 21 (2): 299-310, 1991. [PUBMED Abstract]
Halverson KJ, Perez CA, Kuske RR, et al.: Survival following locoregional recurrence of breast cancer: univariate and multivariate analysis. Int J Radiat Oncol Biol Phys 23 (2): 285-91, 1992. [PUBMED Abstract]
Halverson KJ, Perez CA, Kuske RR, et al.: Isolated local-regional recurrence of breast cancer following mastectomy: radiotherapeutic management. Int J Radiat Oncol Biol Phys 19 (4): 851-8, 1990. [PUBMED Abstract]
Aebi S, Gelber S, Anderson SJ, et al.: Chemotherapy for isolated locoregional recurrence of breast cancer (CALOR): a randomised trial. Lancet Oncol 15 (2): 156-63, 2014. [PUBMED Abstract]
Wapnir IL, Price KN, Anderson SJ, et al.: Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial. J Clin Oncol 36 (11): 1073-1079, 2018. [PUBMED Abstract]