Molecular Clonality Determination of Ipsilateral Recurrence of Invasive Breast Carcinomas After Breast-Conserving Therapy: Comparison With Clinical and Biologic Factors

Abstract

We established clonality relationships between invasive ipsilateral breast failures (IBFs; local recurrences) and initial invasive carcinomas using a molecular polymerase chain reaction loss of heterozygosity (LOH) assay for 26 patients treated with breast-conserving therapy for invasive carcinoma with no distant metastases (DMs) before the IBE LOH was +/- 50% allelic loss. Eighteen IBFs (69%) were related clonally to initial carcinomas; 8 (31%) were clonally distinct, second primary carcinomas. IBFs and initial invasive carcinomas were morphologically similar in 6 (75%) of 8 clonally different cases. Clinical IBF classification and molecular assay results differed in 11 cases (42%). The mean intervals to IBF were 4.7 years in related and 8.7 years in different cases (P = .013). In 6 patients, DMs developed; 5 had related IBFs. In related IBF cases, the mean increase in fractional allelic loss (FAL) of IBFs associated with DMs was 18.9% compared with 7.6% in cases unassociated with DMs (P = .004). Molecular assays can accurately establish the clonality of most IBFs. Morphologic comparison and clinical IBF classification are unreliable methods of determining clonality. Clonally related IBFs occurred sooner than clonally different IBFs. Patients with clonally related IBFs are the main pool in which DMs occur Not all clonally related IBFs have the same DM association; those with large FAL gains were associated with DMs. Molecular clonality assays may provide a reliable means of identifying patients who might benefit from systemic chemotherapy at the time of IBF.

Are ipsilateral breast tumour invasive recurrences in young (⩽40 years) women more aggressive than their primary tumours?

“…Contrary to others (Haffty et al, 1993;Goldstein et al, 2005;Vicini et al, 2007), we found no indication that tumours more prone to be true recurrences because of conserved histological type, location or both, recur sooner or are deadlier than the others. The same applied to the conservation of histological type and features of equal or lesser differentiation.…”

Evaluating distant metastases in breast cancer: from biology to outcomes

“…Patients revealing residual initial local recurrences are at greater risk for DM than patients with de novo, second primary neoplasms [58,59]. Many studies have consistently shown that the annual risk of developing DM increases over a period of 10 years in patients with locoregional recurrences [60][61][62][63].…”

The use of molecular assays to establish definitively the clonality of ipsilateral breast tumor recurrences and patterns of in‐breast failure in patients with early‐stage breast cancer treated with breast‐conserving therapy

“…21,22 Slides of the initial carcinoma and the IBTR carcinoma were reviewed, and foci of invasive or metastatic carcinoma with minimal inflammatory cells were outlined carefully on the slide. Tissues from the corresponding blocks were microdissected carefully with clean scalpel blades and needles using the outlined area on the slide as a template.…”

“…A low LR value reflected a high probability the initial and IBTR carcinomas were different clonally, and were unrelated neoplasms and that the IBTR was a second primary carcinoma. 21,22 Clinical Assessment of the Type of IBTR All IBTRs were evaluated separately (without knowledge of the results of the molecular clonality analyses) by using clinical (and in, some patients, pathologic) criteria to determine whether they represented a new primary cancer versus a recurrence of the index lesion. IBTRs were subdivided into true recurrence/marginal miss (TR/MM) failures versus elsewhere (E) failures based on the location of the recurrence within the breast (Harvard criteria).…”