Multifocal or MultiCentric Breast Cancer

Multiple ipsilateral breast cancers 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
The term 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 multifocal or multicentric breast cancer (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):
    - 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:
        
        They found that BCT was not inferior to mastectomy with respect to 5-year (2.5% vs. 4.5%) and 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):
  - Were 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, and 67% underwent lumpectomy in a single operation
  - Conversion to mastectomy occurred in:
    - 7.1% of patients due to positive margins
  - Results:
    - Among 270 women enrolled between November 2012 and August 2016:
      - There were 204 eligible patients who underwent protocol-directed BCT
    - The median age was 61 years (range, 40 to 87 years)
    - At a median follow-up of 66.4 months (range, 1.3-90.6 months):
      - Six patients developed LR for an estimated 5-year cumulative incidence of LR of:
        
        3.1% (95% CI, 1.3 to 6.4):
        
        Patient age, number of sites of preoperative biopsy–proven BC, estrogen receptor status and human epidermal growth factor receptor 2 status, and pathologic T and N categories were not associated with LR risk
      - Exploratory analysis showed that the 5-year LR rate:
        
        In patients without preoperative magnetic resonance imaging (MRI; n = 15) was 22.6% compared with 1.7% in patients with a preoperative MRI (n = 189; P = .002)
  - Conclusion of the Alliance Z11102:
    - The Z11102 clinical trial demonstrates that breast-conserving surgery with adjuvant radiation that includes lumpectomy site boosts yields an acceptably low 5-year LR rate for MIBC. This evidence supports BCT as a reasonable surgical option for women with two to three ipsilateral foci, particularly among patients with disease evaluated with preoperative breast MRI.
When considering the appropriateness for breast conservation in multiple ipsilateral breast cancers:
- The distance between the lesions, location, and breast size must be considered
Oncoplastic techniques can be considered as needed for an improved cosmetic outcome:
- With good disease-free survival and low risk of local recurrence
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.