Breast Cancer Multifocality and Multicentricity and Locoregional Recurrence

Abstract

Background. The impact of multifocal (MF) or multicentric (MC) breast cancer on locoregional (LR) control rates is unknown. Methods. MF was defined as two or more separate invasive tumors in the same quadrant of the breast. MC was defined as two or more separate invasive tumors occupying more than one quadrant of the same breast. Patients were categorized by LR treatment: breast conservation therapy (BCT; n ϭ 256), mastectomy (n ϭ 466), or mastectomy plus postmastectomy radiation therapy (PMRT; n ϭ 184). All patients with MC disease had mastectomy (10 patients treated with BCT for MC disease were excluded). The Kaplan-Meier product limit method was used to calculate 5-year LR control rate. Cox proportional hazards models were used to determine independent associations of multifocality or multicentricity with LR control.Results. A total of 906 patients had either MF disease (n ϭ 673) or MC disease (n ϭ 233). With median follow-up of 52 months, the 5-year LR control rate was 99% for MF, 96% for MC, and 98% for unifocal tumors (p ϭ .44). Subset analysis revealed no difference in LR control regardless of the LR treatment (p ϭ .67 for BCT, p ϭ .37 for mastectomy, p ϭ .29 for mastectomy plus PMRT). There were five in-breast recurrences after BCT in the MF group. MF and MC did not have an independent impact on LR control rate on multivariate analysis. Conclusion. MF and MC disease are not independent risk factors for LR recurrence. Patients with MF and MC breast cancer had rates of LR control similar to those of their unifocal counterparts. These data suggest that BCT is a safe option for patients with MF tumors and that MF or MC disease alone is not an indication for PMRT. The Oncologist 2013;18:1167-1173 Implications for Practice: This work reviews the risk of locoregional recurrences in patients with breast cancer treated with different approaches, as currently recommended by standard guidelines. We looked at 2,816 cases with unifocal disease, 673 cases with multifocal (MF) disease, and 233 cases with multicentric (MC) disease. We showed that MF and MC breast cancers are not independently associated with increased locoregional recurrence rates and that breast conservation therapy is a safe option for patients with MF tumors. MF or MC disease alone is not an indication for postmastectomy radiation therapy.

Systematic review of the impact of breast‐conserving surgery on cancer outcomes of multiple ipsilateral breast cancers

“…The 24 studies had retrospective observational designs, comprising 17 comparative studies20, 21, 22, 23 27, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 and seven case series28 44, 45, 46, 47, 48, 49 ( Table 1; Table   S1, supporting information). The studies included a total of 3537 women with MIBC undergoing BCS: 2677 with tumours defined as MF, 292 as MC, and 568 not defined as either MF or MC, but reported as MIBC.…”

“…The studies included a total of 3537 women with MIBC undergoing BCS: 2677 with tumours defined as MF, 292 as MC, and 568 not defined as either MF or MC, but reported as MIBC. Assessment of the observational studies using the NOS showed that three20 27, 43 were of high quality (score at least 7) and 1421, 22, 23 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42 of moderate quality (score 4–6) ( Table   S2, supporting information).…”

“…The incidence of clinically and radiologically detected MIBC ranges from 10 to 24 per cent of all breast cancers20, 21, 22, 23, increasing with time from earlier to later studies. This apparent doubling in incidence of MIBC over the 10 years between 1990 and 2000 may be due in part to improved breast imaging (digital mammography, ultrasonography and MRI) and increased screening24.…”

“…Generally, evaluation of the largest cancer using standard immunohistochemical (IHC) biomarkers (oestrogen and progesterone receptors, human epidermal growth factor receptor 2 (HER2) and Ki‐67) is performed3 9, 15. However in future, the potential to use extended IHC biomarkers and whole‐genome sequencing may increase the recognition of intertumoral heterogeneity14 16, 17, 18, with prognostic implications19, 20, 21, 22.…”

“…Standard imaging of MIBC may include digital mammography, ultrasound examination and MRI, with biopsy confirmation of any additional suspected cancers on MRI to minimize their misdiagnosis, which occurs in 30 per cent of ‘lesions’24 25. Studies6 10, 11 19, 20, 21 23, 26 are conflicting on the prognostic implications of MIBC, with suggestions of increased axillary lymph node involvement latterly using sentinel lymph node biopsy (SLNB), and with worse overall outcomes than those for unifocal cancers19 22, 23. Increased rates of locoregional recurrence (LRR)5 and breast cancer events22 23, 27 28 secondary to BCS for MIBC have been reported, but vary widely across studies.…”