Pathological complete response after primary chemotherapy in a mother and daughter with hereditary breast carcinoma: two case reports

The prognosis of patients with BRCA1-related breast carcinomas is inferior to the patients without BRCA1 mutation, but most of these tumors have a so-called triple negative phenotype characterized by increased chemosensitivity. Information regarding the chemosensitivity of BRCA1-related breast carcinomas is limited. We present a case of a mother and daughter with hereditary breast carcinoma treated with primary chemotherapy using the dose-dense combination of doxorubicin and cyclophosphamide and sequential weekly paclitaxel administration. Pathological complete response was observed in both patients. Subsequent genetic analysis revealed the same BRCA1 mutation with exon 5-14 deletion in both women. The present experience as well as other reports indicate increased sensitivity of BRCA1-related breast carcinoma to primary chemotherapy.

Hereditary breast carcinoma; BRCA1; Pathological complete response

[1] Veronesi U., Boyle P., Goldhirsch A., Orecchia R., Viale G.: “Breast cancer”. Lancet, 2005, 365, 1727.

[2] Early Breast Cancer Trialists Collaborative Group: "Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials". Lancet , 2005, 365, 1687.

[3] Estevez L.G., Gradishar W.J.: “Evidence-based use of neoadjuvant taxane in operable and inoperable breast cancer”. Clin. Cancer Res., 2004, 10, 3249.

[4] Kaufmann M., Hortobagyi G.N., Goldhirsch A., Scholl S., Makris A., Valagussa P. et al.: “Recommendations from an international expert panel on the use of neoadjuvant (primary) systemic treatment of operable breast cancer: an update”. J. Clin. Oncol., 2006, 24, 1940.

[5] Chevallier B., Roche H., Olivier J.P., Chollet P., Hurteloup P.: “Inflammatory breast cancer. Pilot study of intensive induction chemotherapy (FEC-HD) results in high histologic response rate”. Am. J. Clin. Oncol., 1993, 16, 223.

[6] Chollet P., Amat S., Cure H., de Latour M., Le Bouedec G., Mouret-Reynier M.A. et al.: “Prognostic significance of a complete pathological response after induction chemotherapy in operable breast cancer”. Br. J. Cancer, 2002, 86, 1041.

[7] Bear H.D., Anderson S., Smith R.E., Geyer C.E., Mamounas E.P., Fischer 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.

[8] Machiavelli M.R., Romero A.O., Perez J.E., Lacava J.A., Domin -guez M.E., Rodriguez R., et al.: “Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma”. Cancer J. Sci. Am., 1998, 4, 125.

[9] Thomas E., Holmes F.A., Smith T.L., Buzdar A.U., Frye D.K., Fraschini G., et al.: “The use of alternate, non-cross-resistant adjuvant chemotherapy on the basis of pathologic response to a neoadjuvant doxorubicin-based regimen in women with operable breast cancer: long-term results from a prospective randomized trial”. J. Clin. Oncol., 2004, 22, 2294.

[10] King M.C., Marks J.H., Mandell J.B.: “Breast and ovarian cancer risks due to inherited mutations in BRCA1 and BRCA2”. Science, 2003, 302, 643.

[11] Robson M.E., Chappuis P.O., Satagopan J., Wong N., Boyd J., Goffin J.R., et al.: “A combined analysis of outcome following breast cancer: differences in survival based on BRCA1/BRCA2 mutation status and administration of adjuvant treatment”. Breast Cancer Res., 2004, 6, R8.

[12] Goffin J.R., Chappuis P.O., Begin L.R., Wong N., Brunet J.S., Hamel N., et al.: “Impact of germline BRCA1 mutations and overexpression of p53 on prognosis and response to treatment following breast carcinoma. 10-year follow-up data”. Cancer, 2003, 97, 527.

[13] Rubin S.C., Benjamin I., Benbakht K., Takahashi H., Morgan M.A., LiVolsi V.A., et al.: “Clinical and pathological features of ovarian cancer in women with germ-line mutations of BRCA1”. N. Engl. J. Med., 1996, 335, 1413.

[14] Boyd J., Sonoda Y., Federici M.G., Bogomolniy F., Rhei E., Maresco D.L., et al.: “Clinicopathologic features of BRCA-linked and sporadic ovarian cancer”. JAMA, 2000, 283, 2260.

[15] Cass I., Baldwin R.L., Varkes T., Moslehi R., Narod S.A., Karlan B.Y.: “Improved survival in women with BRCA-associated ovarian carcinoma”. Cancer, 2003, 97, 2187.

[16] Cleator S., Heller W., Coombes C.R.: “Triple-negative breast cancer: therapeutic options”. Lancet Oncol., 2007, 8, 235.

[17] Chappuis P.O., Goffin J., Wong N., Perret C., Ghadirian P., Tonin P.N., et al.: “A significant response to neoadjuvant chemotherapy in BRCA1/2 related breast cancer”. J. Med. Genet., 2002, 39, 608.

[18] Warner E., Trudeau M., Holloway C.: “Sensitivity of BRCA-1- related breast cancer to neoadjuvant chemotherapy: practical implications”. Breast J., 2003, 9, 507.

[19] Kennedy R.D., Quinn J.E., Mullan P.B., Johnston P.G., Harkin D.P.: “The role of BRCA1 in the cellular response to chemotherapy”. J. Natl. Cancer Inst., 2004, 96, 1659.

[20] Citron M.L., Berry D.A., Cirrincione C., Hudis C., Winer E.P., Gradishar W.J., et al.: “Randomized trial, of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of nodepositive primary breast cancer: first report of Intergroup trial C9741/Cancer and Leukemia Group B trial 9741”. J. Clin. Oncol., 2003, 21, 1431.

[21] Henderson I.C., Berry D., Demetri G., Cirrincione C., Goldstein L., Martino S., et al.: “Improved outcomes from adding sequential paclitaxel but not from the escalating doxorubicin dose in an adjuvant chemotherapy regimen for patients with node-positive primary breast cancer”. J. Clin. Oncol., 2003, 21, 976.

[22] Green M.C., Buzdar A.U., Smith T., Ibrahim N.K., Valero V., Rosales M.F., et al.: “Weekly paclitaxel improves pathologic complete remission in operable breast cancer when compared with paclitaxel with paclitaxel once every 3 weeks”. J. Clin. Oncol., 2005, 23, 5983.