The development of interval breast malignancies in patients with BRCA mutations

Cancer. 2004 May 15;100(10):2079-83. doi: 10.1002/cncr.20221.


Background: At present, there is no consensus regarding how frequently BRCA mutation carriers should be screened for malignancies using breast imaging techniques. An interval malignancy is defined as a malignancy that becomes evident during the period between annual screening mammography scans; the finding of such a malignancy indicates that the malignancy either went undetected by the last breast imaging scan or developed during the interval since that last scan.

Methods: The authors retrospectively reviewed the medical charts of all BRCA mutation carriers who were followed by the genetic counselor at the Columbia-Presbyterian Comprehensive Breast Center (New York, NY) between September 1995 and September 2002.

Results: Thirteen BRCA mutation carriers elected to undergo close surveillance and thus were followed at our institution. Three of these 13 patients (23%) did not develop breast carcinoma, 4 (31%) developed breast carcinoma that was detected at the time of annual screening, and 6 (46%) developed palpable interval malignancies in less than 12 months. Among the six patients who developed interval malignancies, the mean time between the last screening mammogram and disease presentation was 5.1 months (range, 2-9 months); the average tumor size in this patient subgroup was 1.7 cm (range, 0.8-3 cm). Two of these six patients had ductal carcinoma in situ, whereas the remaining four had invasive breast carcinoma; three patients had positive lymph nodes at presentation. All six patients who developed interval disease exhibited dense breast tissue on the previous mammogram. Focused breast ultrasonography was able to identify the tumor mass in 3 of 4 patients (75%).

Conclusions: Nearly half of all BRCA-positive women who chose to undergo close surveillance in the current study developed malignant disease less than a year after exhibiting normal findings on screening mammography. Half of these interval malignancies were positive for lymph node involvement. These results suggest that strong consideration should be given to screening BRCA-positive women at more frequent intervals and to using additional imaging techniques, such as breast ultrasonography and/or breast magnetic resonance imaging, as a part of this screening.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / pathology
  • Carcinoma, Intraductal, Noninfiltrating / genetics
  • Carcinoma, Intraductal, Noninfiltrating / pathology
  • Female
  • Genes, BRCA1*
  • Genes, BRCA2*
  • Humans
  • Incidence
  • Mastectomy
  • Middle Aged
  • Mutation*
  • Neoplasm Invasiveness
  • Retrospective Studies
  • Time Factors