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Professor Roland Holland: How Patterns of Breast Cancer Influence Therapy

The trend in the past 20 years in the management of patients with breast cancer was to reduce the extent of treatment without limiting its effectiveness.

Clinical trials with long term follow-up have demonstrated that for appropriately selected patients, breast conserving surgery followed by whole breast irradiation has an outcome equivalent to mastectomy. Further, it has been recently proposed the technique of accelerated partial breast irradiation (APBI) instead of whole breast irradiation based on the observation that most breast cancers are limited to one quadrant or to a limited area of the breast. The target volume for ABPI is usually the surgical cavity and a 1- to 2-cm margin around this cavity. This implies that the total size of the diseased area (dominant mass and potential multifocal tumour foci around it), should not extend beyond a 1- to 2-cm margin from the dominant mass.

The Nijmegen whole organ studies disclosed that although breast cancers are often multifocal only less than 10% have a so-called multicentric distribution defined as the presence of two or more foci of cancers separated by a 3- to 4-cm uninvolved glandular tissue. Thus, on the other hand, around 90% of breast cancers are unicentric, i.e. limited to one single quadrant or breast region. This morphological observation is supported by the clinical data of follow-up after breast-conserving therapy, i.e. focal tumour recurrence appears in 90% within the operated quadrant. About 60% of breast cancers are multifocal having additional microscopic tumour foci, usually DCIS, around the invasive tumour mass, but about 40% are unifocal without such additional tumour foci. This latter group of tumours are the potential candidates for APBI after the surgical excision of the tumour. Even some of the multifocal tumours could be candidates for APBI, provided that the additional foci around the invasive tumour mass are limited to a 1- to 2-cm margin around the tumour.

We studied the mammographic and pathological criteria for the identification of such breast carcinomas with limited extent (BCLE). Surgical breast-conserving procedures were simulated in a review of 135 mastectomy specimens of patients treated for invasive carcinoma (= 4cm in size) who were theoretically eligible for conservative treatment. Tumour spread including multifocality and multicentricity was studied by the technique of correlated specimen radiography and pathology. Breast carcinoma of limited extent was defined as having no invasive carcinoma, DCIS and lymphatic involvement foci beyond 1 cm from the edge of the dominant mass.

The 1-cm margin was not arbitrarily chosen but is in accordance with the current attitude of surgeons to excise the tumour with at least a 1-cm grossly uninvolved margin in breast-conserving procedures.

The results of the study showed that 53% of patients in this series had a BCLE. Based on mammography, the absence of microcalcifications or tumour density beyond the edge of the dominant tumour appears to be the best predictor for BCLE (p <.0001). Based on pathology, a 1-cm microscopically tumour free margin as the outer rim of a gross surgical margin of 2 cm gives the best positive predictive value for the identification of BCLE (p <.0001).

By applying the above mammographic and pathologic conditions, 72 of the 135 cancers were identified as being potential BLCE cases. However, while 64 of these 72 tumours (89%) were correctly identified as being true BCLE, 8 (11%) cases were erroneously identified as such, having residual tumour foci beyond 2 cm from the edge of the dominant tumour.

We conclude, that approximately 50% of invasive ductal carcinomas could have limited extent. The identification of this group of cancers is possible by applying optimal quality mammography and by the meticulous pathological assessment of the surgical specimen. These breast cancers with limited extent could be the potential candidates for the treatment of surgical excision of the tumour followed by partial breast irradiation.

Considering that these conclusions are based on a morphologic model, clinical studies with facilities for high quality team approach in diagnosis and therapy are needed to validate the above results.