Multiple Ipsilateral Breast Cancers (MIBC)

Multiple ipsilateral breast cancers (MIBC) include:
- Both multifocal and multicentric disease
The term multifocal (MF):
- Typically refers to two or more foci of disease within a single quadrant of the breast,
Multicentric (MC):
- Refers to two or more foci in more than one quadrant of the breast
When staging:

An “m” modifier, is added to TNM classification to identify MF / MC disease

In the setting of MIBC:
- The size of the largest focus is used for staging:
  - Rather than a cumulative measurement of the tumor sizes
Historically, it was believed that multiple ipsilateral breast cancers should be treated surgically with mastectomy:
- This thought is based on early retrospective studies (1980s-90s):L
  - That reported a higher locoregional recurrence (LRR) in patients with MF / MC disease who underwent breast conserving therapy (BCT)
- More current studies, which include patients treated in a contemporary multidisciplinary setting:
  - Have demonstrated a more promising role for BCT in MF / MC disease
  - A systematic review included six retrospective studies evaluating patients with multiple ipsilateral breast cancers undergoing BCT vs. mastectomy:
    - The rate of LRR overall was 2% to 23% for BCT:
      - With similar rates of LRR for BCS compared to mastectomy
    - The largest of these compared 887 patients who underwent mastectomy vs. 300 who underwent BCT:
      - And found that BCT was not inferior to mastectomy:
        With respect to:
        5-year (2.5% vs. 4.5%) LRR
        10-year (6.5% vs 5.7%) LRR
In a study reviewing surgical management of 6,134 patients undergoing neoadjuvant chemotherapy:
- 1,401 (23%) were found to have MF / MC disease
- 617 patients (44%) underwent BCT
- Local recurrence-free survival, disease-free survival (DFS), and overall survival (OS):
  - We’re not inferior in patients with MF / MC compared with unifocal disease:
    - If negative margins or a pathologic complete response was obtained
In a study evaluating 110 patients with MF / MC disease compared to 263 matched-case controls with unifocal disease:
- MF / MC disease had worse local control and DFS:
  - But was not impacted by the type of surgery performed
The heterogeneity of findings related to the management of multiple ipsilateral breast cancers underscores the need for a prospective clinical trial to address this issue:
- The Alliance Z11102 prospective trial aimed to evaluate the feasibility and safety of breast conservation in women with multiple ipsilateral breast cancers:
  - Defined as having tumors separated by 2 cm or more of normal breast tissue:
    - The authors found that of the 198 patients enrolled:
      - 93% underwent successful lumpectomy:
        67% underwent lumpectomy in a single operation
      - Conversion to mastectomy occurred in 7.1% of patients due to positive margins
      - Primary endpoint is LRR at 5 years, and these results will be forthcoming as the data mature
Thus, based on available data:
- MF / MC is not an absolute contraindication to BCT
Oncoplastic techniques:
- Can be considered as needed for an improved cosmetic outcome, with high rates with disease-free survival and low risk of local recurrence
Chemotherapy can be given as her primary treatment:
- Which may improve her surgical options
References
Kurtz JM, Jacquemier J, Amalric R, et al. Breast-conserving therapy for macroscopically multiple cancers. Ann Surg. 1990;212(1):38-44.
Winters ZE, Horsnell J, Elvers KT et al. Systematic review of the impact of breast-conserving surgery on cancer outcomes of multiple ipsilateral breast cancers. BJS Open. 2018;2(4):162-174. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069349/. Accessed August 25, 2019.
Yerushalmi R, Tyldesley S, Woods R, et al. Is breast-conserving therapy a safe option for patients with tumor multicentricity and multifocality? Ann Oncol. 2012;23(4):876-881.
Ataseven B, Lederer B, Blohmer JU, et al. Impact of multifocal or multicentric disease on surgery and locoregional, distant and overall survival in 6134 breast cancer patients treated with neoadjuvant chemotherapy. Ann Surg Oncol. 2015;22(4):1118–1127.
Shaikh T, Tam T, Li T, et al. Multifocal and multicentric breast cancer is associated with increased local recurrence regardless of surgery type. Breast J. 2015;21(2):121-126.
Rosenkranz, K.M., Ballman, K., McCall, L. et al. The feasibility of breast-conserving surgery for multiple ipsilateral breast cancer: an initial report from ACOSOG Z11102 (Alliance) Trial. Ann Surg Oncol. 2018;25(10):2858-2866.
De La Cruz L, Blakenship SA, Chatterjee A, et al. Outcomes after oncoplastic breast-conserving surgery in breast cancer patients: a systematic literature review. Ann Surg Oncol. 2016;23(10):3247-3258.
Rastogi P, Anderson SJ, Bear HD. Preoperative chemotherapy: updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27. J Clin Oncol. 2008;10;26(5):778-785.