Lobular Carcinoma in Situ (LCIS) in Association with Invasive Breast Cancer: Does LCIS Predict for Local Recurrence?

Reviewer: Voika BarAd, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: October 18, 2005

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Presenter: S. Jolly
Presenter's Affiliation: Radiation Oncology, William Beaumont Hospital, Royal Oak, MI, Pathology, William Beaumont Hospital, Royal Oak, MI
Type of Session: Scientific

Background

  • More than 5% of malignant breast cancers have a component of LCIS.
  • The association of LCIS with invasive breast cancer for patients undergoing breast-conserving therapy (BCT).
  • Recent data indicates that LCIS may have substantial premalignant potential and progress to invasive cancer, in addition to functioning as a general risk factor for subsequent invasive breast cancer.
  • The study investigates the impact of LCIS on clinical outcome in patients with invasive breast carcinoma who are treated with BCT.

Materials and Methods

  • 607 patients with invasive breast cancer were treated with lumpectomy followed by radiotherapy to median total dose of 61 Gy, from 1980 to 1996.
  • All slides from each case underwent complete pathologic review by a single pathologist.
  • A positive margin was defined as the presence of invasive carcinoma or ductal carcinoma in situ (DCIS) at the inked margin.
  • The margin status was classified as negative for all other cases, including those cases with margin distance of < 2 mm..

Results

  • The median follow-up was 8.7 years.
  • The median age of all patients was 61 years.
  • 56 patients (9%) demonstrated the presence of LCIS in the specimen.
  • The presence of LCIS was associated with lower grade carcinoma, larger maximum specimen dimension, and the absence of DCIS.
  • On univariate analysis, factors predicting for ipsilateral breast failure included positive final margins, positive margin with no reexcision (vs. a negative reexcision), smaller maximum specimen dimension, and the presence of LCIS.
  • The 10 year ipsilateral breast failure rate was 14% for cases with LCIS vs 7% for cases without LCIS, which was a statistically significant difference.
  • When examining only those 559 cases with negative final margins, the 10 year ipsilateral breast failure rate was 14% for cases with LCIS vs 4% for cases without LCIS.
  • 84% of ipsilateral breast failures in LCIS-positive cases were invasive ductal carcinomas.
  • Cases with LCIS in the initial excision were significantly less likely to have residual invasive carcinoma or DCIS at reexcision (50% positive reexcision with LCIS in the initial excision vs 67% without LCIS). This further implies that residual LCIS could possibly be responsible for local recurrence, and not a component of residual DCIS or invasive carcinoma.

Author's Conclusions

  • The presence of LCIS was independently associated with ipsilateral breast failure following BCT for invasive breast cancer. This suggests that LCIS may have significant premalignant potential and may progress to an invasive ipsilateral breast failure.
  • LCIS associated with invasive carcinoma may have significant premalignant potential that is similar to low-grade DCIS and which is more substantial than incidental LCIS alone (without invasive).
  • The presence of LCIS, as well as the adequacy of excision of LCIS that is associated with invasive carcinoma, should be considered following lumpectomy.

Clinical/Scientific Implications

  • LCIS has traditionally been considered to only be a risk factor for subsequent breast carcinoma, rather than a precursor, or premalignant lesion.
  • This trial demonstrates the premalignant potential of LCIS and its possible capacity to progress to invasive cancer, in addition to functioning as a general risk factor for subsequent invasive breast cancer.
  • If we suggest that LCIS has a premalignant potential similar to low-grade DCIS, the next question is whether, in the future, we will treat LCIS of the breast in a similar way as we treat DCIS? This remains a challenging question with no clear answer at this time, but represents an area for further research.
  • The pathological distinction between LCIS and low-grade DCIS can be difficult.
  • Several reports have suggested the possibility that invasive ductal and invasive lobular carcinomas of the breast differ with respect to expression of antigens involved in proliferation and cell cycle regulation. Few papers, however, describe the immunohistochemical markers useful for differentiation of these carcinomas.
  • Future studies, using immunohistochemical techniques, will validate the role of LCIS in the clinical outcome of patients with invasive breast carcinoma.