DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20151241

Study on the role of primary systemic chemotherapy with anthracycline combination schedule in locally advanced breast cancer: long term follow up data

Aravindh S. Anand

Abstract


Background: Locally advanced breast cancer (LABC) refers to a heterogeneous group of locally advanced non metastatic group of breast cancer. Primary systemic chemotherapy (PST) which forms the prime modality in LABC management has several advantages. The objective of the study was to assess the response and survival of locally advanced breast cancer patients receiving PST with Anthracycline based combination chemotherapy in Indian setting.

Methods: 75 LABC patients who were treated with PST were observed and finally analyzed for survival. Chemotherapy schedules were FAC (5-Fluorouracil 500 mg/m2, Doxorubicin 50 mg/m2 and Cyclophosphamide 500 mg/m2) and FEC (5-Fluorouracil 500 mg/m2, Epirubicin 100 mg/m2 and Cyclophosphamide 500 mg/m2).Clinical complete response (cCR), partial response (PR), stable disease (SD) and pathological complete response (pCR) were assessed. 5 year overall survival (O.S) & disease free survival (DFS) were analyzed using Kaplan Meier survival analysis.

Results: 94% became operable after PST and 6% remained inoperable. MRM with axillary clearance was achieved in 70.4% while simple mastectomy with axillary dissection in 22.5%. Microscopic surgical clearance achieved in 85.9%. Objective clinical tumour response rate was 78.9% with cCR of 11.3%, PR of 67.6% & pCR of 7.5%. Five year O.S and DFS were 67.92% and 62.21% respectively.

Conclusions: Anthracycline based chemotherapy is an excellent schedule in neoadjuvant setting in LABC in down staging disease. But to further improve the O.S, DFS and pCR addition of agents like Taxanes and their sequencing must be explored. RCTs addressing these issues are warranted especially in countries like India.

 


Keywords


Locally advanced breast cancer, Primary systemic chemotherapy, Tumour response, Survival

Full Text:

PDF

References


AJCC Cancer Staging Manual, 7th edition, 2010

Bonadonna G, Valagussa P, Brambilla C, Ferari L, Moliterni A, Terenziani M, et al. Primary chemotherapy in operable breast cancer: Eight- years’ experience at the Milan Cancer Institute. J Clin Oncol. 1998;16:93-100.

Skipper HE. Adjuvant chemotherapy. Cancer1978; 41:936-40 Powles TJ, Hickish TF, Makris A et al. Randomized trial of chemo endocrine therapy before or after surgery for treatment of primary breast cancer. J Clin Oncol. 1995;13:547-52.

Powles TJ, Hickish TF, Makris A. Randomized trial of chemo-endocrine therapy before or after surgery for treatment of primary breast cancer. J Clin Oncol. 1995;13:547-52.

Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al. Effect of preoperative chemotherapy on the outcome of women with operable breast cancer. J Clin Oncol. 1998;16:2672-85.

Semiglazov VF, Topuzov EE, Bavli JL. Primary (neoadjuvant) chemotherapy and radiotherapy compared with primary radiotherapy alone in stage IIb-IIIa breast cancer. Ann Oncol. 1994;5:591-5.

van der Hage JA, van de Velde CJ, Julien JP. Preoperative chemotherapy in primary operable breast cancer: results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19:4224-37.

Van der Hage JA, Van de Velde CT, Julien JP, Tubiana-Hulin M, Vandervelden C, Duchateau L. Preoperative chemotherapy in primary operable breast cancer: Results from the European Organization for Research and Treatment of Cancer trial 10902. J Clin Oncol. 2001;19:4224-37.

Fisher B, Bryant J, Wolmark N, Mamounas E, Brown A, Fisher ER, et al. Effect of preoperative chemotherapy on outcome of women with operable breast cancer. J Clin Oncol. 1998;16:2672-85.

Cancer WG, Carey LA, Calvo BF, Sartor C, Sawyer L, Moore DT, et al. Long-term outcome of neoadjuvant chemotherapy for locally advanced breast carcinoma: Effective clinical down staging allows breast preservation and predicts outstanding local control and survival. Ann Surg. 2002;236:295-303.

Chen AM, Meric-Bernstam F, Hunt KK, Thames HD, Oswald MJ, Outlaw ED, et al. Breast conservation after neoadjuvant chemotherapy: The MD Anderson Cancer Center experience. J Clin Oncol. 2004;22:2303-12.

Kuerer HM, Sahin AA, Hunt KK, Newman LA, Breslin TM, Ames FC, et al . Incidence and impact of documented eradication of breast cancer axillary lymph node metastases before surgery in patients treated with neoadjuvant chemotherapy. Ann Surg. 1999;230:72-8.

Heys SD, Hutcheon AW, Sarkar TK, Ogston KN, Miller ID, Payne S, et al. Neoadjuvant docetaxel in breast cancer: 3-year survival results from the Aberdeen trial. Clin Breast Cancer. 2002;3:S69-74.

Smith IC, Heys SD, Hutcheon AW, Miller ID, Payne S, Gilbert FJ, et al. Neoadjuvant chemotherapy in breast cancer: Significantly enhanced response with docetaxel. J Clin Oncol. 2002;20:1456-66.

Luporsi E, Vanlemmens L, Coudert B. Six cycles of FEC 100 vs 6 cycles of Epirubicin-docetaxel (ED) as neoadjuvant chemotherapy in operable breast cancer patients (Pts): Preliminary results of a randomized phase II trial of GIREC S01. J Clin Oncol. 2000;18:19.

Bear HD, Anderson S, Brown A, Smith R, Mamounas EP, Fisher B, et al. The effect on tumor response of adding sequential preoperative docetaxel to preoperative doxorubicin and cyclophosphamide: Preliminary results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2003;21:4165-74.

Bear HD, Anderson S, Smith RE, Geyer CE Jr, Mamounas EP, Fisher B, et al. Sequential preoperative or postoperative docetaxel added to preoperative doxorubicin plus cyclophosphamide for operable breast cancer: National Surgical Adjuvant Breast and Bowel Project Protocol B-27. J Clin Oncol. 2006;24:2019-27.

Evans TR, Yellowlees A, Foster E, Earl H, Cameron DA, Hutcheon AW, et al. Phase III randomized trial of doxorubicin and docetaxel versus doxorubicin and cyclophosphamide as primary medical therapy in women with breast cancer: An anglo-celtic cooperative oncology group study. J Clin Oncol. 2005;23:2988-95.

Agarwal G, Pradeep PV, Agarwal V, Yip CH, Cheung PS. Spectrum of breast cancer in Asian women. World J Surg. 2007;31:1031-40.

El Saghir NS, Khalil MK, Eid T. Trends in epidemiology and management of breast cancer in developing Arab countries: a literature and registry analysis. Int J Surg. 2007;5:225-33.

Fregene A, Newman LA. Breast cancer in sub-Saharan Africa: how does it relate to breast cancer in African-American women? Cancer. 2005;103:1540-50.

Rodriguez-Cuevas S, Macias CG, Franceschi D, Labastida S. Breast carcinoma presents a decade earlier in Mexican women than in women in the United States or European countries. Cancer. 2001;91:863-8.

Swain SM, Sorace RA, Bagley CS. Neoadjuvant chemotherapy in the combined modality approach of locally advanced non metastatic breast cancer. Cancer Res. 1987;47:3889-94.

Perloff M, Lesnick GJ, Korzun A. Combination chemotherapy with mastectomy or radiotherapy for stage III breast carcinoma: a Cancer and Leukemia Group B study. J Clin Oncol. 1988;6:261-9.

Hortobagyi GN, Ames FC, Buzdar AU. Management of stage III primary breast cancer with primary chemotherapy, surgery, and radiation therapy. Cancer. 1988;62:2507-16.

Bonadonna G, Veronesi U, Brambilla C. Primary chemotherapy to avoid mastectomy in tumors with diameters of three centimeters or more. J Nat’l Cancer Inst. 1990;82:1539-45.

Jacquillat C, Baillet F, Weil M. Results of a conservative treatment combining induction (neoadjuvant) and consolidation chemotherapy, hormone therapy, and external and interstitial irradiation in 98 patients with locally advanced breast cancer (IIIA-IIIB). Cancer. 1988;61:1977-82.

Pierce LJ, Lippman M, Ben-Baruch N. The effect of systemic therapy on local-regional control in locally advanced breast cancer. Int J Radiat Oncol Biol Phys. 1992;23:949-60.

Schwartz GF, Birchansky CA, Komarnicky LT. Induction chemotherapy followed by breast conservation for locally advanced carcinoma of the breast. Cancer. 1994;73:362-9.

Fisher B, Brown A, Mamounas E. Effect of preoperative chemotherapy on local-regional disease in women with operable breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-18. J Clin Oncol. 1997;15:2483-93.