Familial Cancer

, Volume 1, Issue 2, pp 65–72

Familial breast cancer: an investigation into the outcome of treatment for early stage disease

  • Diana Eccles
  • Peter Simmonds
  • Jonathan Goddard
  • Marie Coultas
  • Shirley Hodgson
  • Fiona Lalloo
  • Gareth Evans
  • Neva Haites


The purpose of this study was to retrospectively compare the outcomes of treatment in 304 women with familial and sporadic breast cancer to clarify the options for the primary management of familial breast cancer. The majority of women were consecutively ascertained on the basis of either breast cancer diagnosed at age < 40 years or bilateral breast cancer. In addition, known BRCA1 mutation carriers were identified through the genetics services in participating centres. These patients were subdivided into those with a significant family history of breast cancer or known BRCA1 mutation (FH+) and those with no significant family history (FH−). There were no significant differences in age, surgical treatment or adjuvant treatment between the two groups, but there were significantly more women whose nodal status was unknown in the FH+ group. Ipsilateral recurrence occurred in 22.2% of FH+ patients compared with 24.1% of FH− patients (p = 0.774) who underwent breast conserving surgery. There was a striking excess of contralateral breast cancers in the FH+ group (35.9% v 16%, p = 0.0007), with a cumulative risk of contralateral cancer of 36% at 10 years. This was reflected in a non-significant trend toward worse relapse free survival in the FH+ group (p = 0.0563), but no difference was observed in overall survival between the two patient groups (p = 0.142). Similarly, for patients with known BRCA1 mutations, contralateral recurrence occurred more frequently, but other outcomes were not significantly different from the FH− group. Breast conserving treatment is not associated with an increased risk of local recurrence in women with familial breast cancer and the prognosis of these women appears to be similar to that of young women with apparently sporadic breast cancer. However, the risk of contralateral breast cancer is significant in the FH+ group and should be considered in planning primary treatment and follow up.

BRCA1 breast cancer familial recurrence survival 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Ford D, Easton DF, Bishop DT et al. Risks of cancer in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Lancet 1994; 343(8899): 692-5.Google Scholar
  2. 2.
    Robson M, Gilewski T, Haas B et al. BRCA-associated breast cancer in young women. J Clin Oncol 1998; 16(5): 1642-9.Google Scholar
  3. 3.
    Verhoog LC, Brekelmans CT, Seynaeve C et al. Survival and tumour characteristics of breast-cancer patients with germline mutations of BRCA1. Lancet 1998; 351: 316-21.Google Scholar
  4. 4.
    Breast Cancer Linkage Consortium. Pathology of familial breast cancer: differences between breast cancers in carriers of BRCA1 or BRCA2 mutations and sporadic cases. Lancet 1997; 349: 1505-10.Google Scholar
  5. 5.
    Marcus JN, Watson P, Page DL et al. BRCA2 hereditary breast cancer pathophenotype. Breast Cancer Res Treat 1997; 44(3): 275-7.Google Scholar
  6. 6.
    Lakhani SR, Jacquemier J, Sloane JP et al. Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations [see comments]. J Natl Cancer Inst 1998; 90(15): 1138-45.Google Scholar
  7. 7.
    Armes JE, Egan AJ, Southey MC et al. The histologic phenotypes of breast carcinoma occurring before age 40 years in women with and without BRCA1 or BRCA2 germline mutations: a population-based study [see comments]. Cancer 1998; 83(11): 2335-45.Google Scholar
  8. 8.
    Karp SE, Tonin PN, Begin LR et al. Influence of BRCA1 mutations on nuclear grade and estrogen receptor status of breast carcinoma in Ashkenazi Jewish women. Cancer 1997; 80(3): 435-41.Google Scholar
  9. 9.
    Hakansson S, Johannsson O, Johansson U et al. Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer. Am J Hum Genet 1997; 60(5): 1068-78.Google Scholar
  10. 10.
    Stoppa-Lyonnet D, Ansquer Y, Dreyfus H, et al. Familial invasive breast cancers: worse outcome related to BRCA1 mutations. J Clin Oncol 2000; 18: 4053-4059Google Scholar
  11. 11.
    Agnarsson BA, Jonasson JG, Bjornsdottir IB et al. Inherited BRCA2 mutation associated with high grade breast cancer. Breast Cancer Res Treat 1998; 47(2): 121-7.Google Scholar
  12. 12.
    Chen JJ, Silver D, Cantor S et al. BRCA1, BRCA2, and Rad51 operate in a common DNA damage response pathway. Cancer Res 1999; 59(7 Suppl): 1752s-6s.Google Scholar
  13. 13.
    Abbott DW, Freeman ML, Holt JT. Double-strand break repair deficiency and radiation sensitivity in BRCA2 mutant cancer cells. J Natl Cancer Inst 1998; 90: 978-85.Google Scholar
  14. 14.
    Scully R, Chen J, Plug A et al. Association of BRCA1 with Rad51 in mitotic and meiotic cells. Cell 1997; 88(2): 265-75.Google Scholar
  15. 15.
    Lim DS, Hasty P. A mutation in mouse rad51 results in an early embryonic lethal that is suppressed by a mutation in p53. Mol Cell Biol 1996; 16(12): 7133-43.Google Scholar
  16. 16.
    Garber J. Inherited breast cancer: increasingly familiar territory. J Clin Oncol 1998; 16(5): 1639-41.Google Scholar
  17. 17.
    Chappuis PO, Kapusta L, Begin LR, et al. Germline BRCA1/2 mutations and p27Kip1 protein levels independently predict outcome after breast cancer. J Clin Oncol 2000; 18: 4045-4052Google Scholar
  18. 18.
    Foulkes WD, Wong N, Brunet JS et al. Germ-line BRCA1 mutation is an adverse prognostic factor in Ashkenazi Jewish women with breast cancer. Clin Cancer Res 1997; 3(12 Pt 1):2465-9.Google Scholar
  19. 19.
    Robson M, Levin D, Federici M et al. Breast Conservation therapy for invasive breast cancer in Ashkenazi women with BRCA gene founder mutations. J Natl Cancer Inst 1999; 91: 2112-7.Google Scholar
  20. 20.
    Porter DE, Cohen BB, Wallace MR et al. Breast cancer incidence, penetrance and survival in probable carriers of BRCA1 gene mutation in families linked to BRCA1 on chromosome 17q12-21. Br J Surg 1994; 81(10): 1512-5.Google Scholar
  21. 21.
    Lee JS, Wacholder S, Struewing JP et al. Survival after breast cancer in Ashkenazi Jewish BRCA1 and BRCA2 mutation carriers. J Natl Cancer Inst 1999; 91(3): 259-63.Google Scholar
  22. 22.
    Johannsson OT, Ranstam J, Borg A, Olsson H. Survival of BRCA1 breast and ovarian cancer patients: a population-based study from southern Sweden. J Clin Oncol 1998; 16(2): 397-404.Google Scholar
  23. 23.
    Eccles DM, Englefield P, Soulby MA, Campbell IG. BRCA1 mutations in southern England. Br J Cancer 1998; 77(12): 2199-203.Google Scholar
  24. 24.
    Peto J, Collins N, Barfoot R et al. Prevalence of BRCA1 and BRCA2 gene mutations in patients with early-onset breast cancer. J Natl Cancer Inst 1999; 91(11): 943-9.Google Scholar
  25. 25.
    Fourquet A, Campana F, Zafrani B et al. Prognostic factors of breast recurrence in the conservative management of early breast cancer: a 25-year follow-up. Int J Radiat Oncol Biol Phys 1989; 17(4): 719-25.Google Scholar
  26. 26.
    Kurtz JM, Amalric R, Brandone H et al. Local recurrence after breast-conserving surgery and radiotherapy. Frequency, time course, and prognosis. Cancer 1989; 63(10): 1912-7.Google Scholar
  27. 27.
    Harris JR, Recht A, Amalric R et al. Time course and prognosis of local recurrence following primary radiation therapy for early breast cancer. J Clin Oncol 1984; 2(1): 37-41.Google Scholar
  28. 28.
    Gage I, Recht A, Gelman R et al. Long-term outcome following breast-conserving surgery and radiation therapy. Int J Radiat Oncol Biol Phys 1995; 33(2): 245-51.Google Scholar
  29. 29.
    Recht A, Silen W, Schnitt SJ et al. Time-course of local recurrence following conservative surgery and radiotherapy for early stage breast cancer. Int J Radiat Oncol Biol Phys 1988; 15(2): 255-61.Google Scholar
  30. 30.
    Kurtz JM, Spitalier JM, Amalric R et al. The prognostic significance of late local recurrence after breast-conserving therapy. Int J Radiat Oncol Biol Phys 1990; 18(1): 87-93.Google Scholar
  31. 31.
    Turner BC, Harrold E, Matloff E et al. BRCA1/BRCA2 germline mutations in locally recurrent breast cancer patients after lumpectomy and radiation therapy: implications for breast conserving management in patients with BRCA1/BRCA2 mutations. J Clin Oncol 1999; 17(10): 3017-24.Google Scholar
  32. 32.
    Chabner E, Nixon A, Gelman R et al. Family history and treatment outcome in young women after breast-conserving surgery and radiation therapy for early-stage breast cancer. J Clin Oncol 1998; 16(6): 2045-51.Google Scholar
  33. 33.
    Pierce L, Strawderman M, Narod S et al. No deleterious effects of radiotherapy in women who are heterozygote for a BRCA-1 or BRCA-2 mutation following breast-conserving therapy. Proc ASCO 1999; 18: 86a (abstr 326).Google Scholar
  34. 34.
    Easton DF, Ford D, Bishop DT. Breast and ovarian cancer incidence in BRCA1-mutation carriers. Breast Cancer Linkage Consortium. Am J Hum Genet 1995; 56(1): 265-71.Google Scholar
  35. 35.
    Boice JD. Cancer following medical irradiation. Cancer 1981; 47(5 Suppl): 1081-90.Google Scholar
  36. 36.
    Fisher B, Costantino JP, Wickerham DL et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 1998; 90(18): 1371-88.Google Scholar
  37. 37.
    Johannsson OT, Idvall I, Anderson C et al. Tumour biological features of BRCA1-induced breast and ovarian cancer. Eur J Cancer 1997; 33(3): 362-71.Google Scholar
  38. 38.
    Verhoog LC, Brekelmans CT, Seynaeve C et al. Survival in hereditary breast cancer associated with germline mutations of BRCA2. J Clin Oncol 1999; 17(11): 3396-402.Google Scholar
  39. 39.
    Osin P, Crook T, Powles T et al. Hormone status of in-situ cancer in BRCA1 and BRCA2 mutation carriers. Lancet 1998; 351(9114): 1487.Google Scholar
  40. 40.
    Osin P, Gusterson BA, Philp E et al. Predicted anti-oestrogen resistance in BRCA-associated familial breast cancers. Eur J Cancer 1998; 34(11): 1683-6.Google Scholar
  41. 41.
    Marcus JN, Watson P, Page DL et al. Hereditary breast cancer: pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage. Cancer 1996; 77(4): 697-709.Google Scholar
  42. 42.
    Verhoog LC, Brekelmans CTM, Seynaeve C et al. Survival in hereditary breast cancer associated with germline mutations of BRCA2. J Clin Oncol 1999; 17(11): 3396-402.Google Scholar
  43. 43.
    Hartmann LC, Schaid DJ, Woods JE et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999; 340(2): 77-84.Google Scholar

Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Diana Eccles
    • 1
  • Peter Simmonds
    • 2
  • Jonathan Goddard
    • 3
  • Marie Coultas
    • 1
  • Shirley Hodgson
    • 4
  • Fiona Lalloo
    • 5
  • Gareth Evans
    • 5
  • Neva Haites
    • 6
  1. 1.Department of Human GeneticsSouthampton University Hospitals NHS TrustUK
  2. 2.CRC Wessex Medical Oncology UnitSouthampton University Hospitals NHS TrustUK
  3. 3.Health Care Research UnitUniversity of SouthamptonUK
  4. 4.Guy's HospitalLondonUK
  5. 5.Regional Genetics ServiceSt Mary's HospitalManchesterUK
  6. 6.Medical SchoolUniversity of AberdeenAberdeenUK

Personalised recommendations