IN NODE NEGATIVE BREAST CANCER WITH DCIS TAKE A SECOND LOOK

May 9, 2012 — Breast cancer patients with node-negative disease and ductal carcinoma in situ (DCIS) should routinely have a secondary pathology review, according to a retrospective Canadian study.

The authors found that 81 of 405 (20%) such patients had changes made to their pathology report after a second look. Ultimately, treatment was modified for 25 patients (6%).

This study, published online May 7 in the Journal of Clinical Oncology, was conducted by researchers from the British Columbia Cancer Agency (BCCA), in Canada, and used the BCCA database of breast cancer patients.

"The reported rates of change...are significant enough to warrant targeted review in this patient population," write the authors, led by Hagen Kennecke, MD, from the BCCA.

The BCCA has an established policy of taking a second look at biopsied tissue in node-negative and DCIS patients in British Columbia, which has 4.4 million residents. The authors explain the policy's importance.

"Because not all patients with node-negative disease are offered chemotherapy or postmastectomy radiation, a change in pathology may result in a significant change in therapy," they write.

The findings "should serve as a wake-up call for treating physicians," according to 2 experts who wrote an accompanying editorial.

In effect, this study, which looked at time periods in 2004 and 2007, was a check-up on the BCCA's mandated pathology approach

Ira Bleiweiss, MD, and George Raptis, MD, both from the Mount Sinai School of Medicine in New York City, note that "some changes in pathology are not surprising," especially a change in grade, which is so subjective and was most common in the study, accounting for 40% of the pathology changes. The second most common change was in lymphovascular invasion status (26%).

The study also looked at changes in margin and nodal status, which are "less expected." The editorialists highlight the fact that 15 of the 81 patients were upstaged from node-negative to node-positive disease, most without the use of immunohistochemical stains.

However, Drs. Bleiweiss and Raptis suggest that changes to the margin status of 12 patients is an upsetting finding. "It is disturbing, but not surprising, that 11 of the 12 cases that involved margin changes were from negative to positive. Depending on individual circumstances, in some practices this might require the patient to be referred back to the surgeon for reexcision," they write.

The editorialists approve of the BCCA's policy of a secondary pathology review for node-negative breast cancers and DCIS.

"Many medical centers require (and, we believe, rightly so) pathology review of outside material before surgery," they write.

The editorialists also believe that the study "does not go far enough" in its scope. The study should have looked at relative costs, they say, because if "rereview prevents more procedures and treatments than it causes, it would be cost effective and better for the patients involved."

Important Even With Gene-Expression Signature

A secondary pathology review is important in node-negative patients even in the era of gene-expression signature tests, the authors explain.

They acknowledge that a "significant proportion of the changes on pathology review were related to measures of tumor biology," including tumor grade and the presence or absence of lymphovascular invasion. "An estimate of tumor biology and responsiveness to adjuvant chemotherapy may also be obtained from tumor gene signatures such as Oncotype DX," they observe.

However, all but 2 of the management changes — which are distinct from the changes on pathology review — were related to changes in nodal, margin, or invasive status, or occurred in initially estrogen-receptor-negative tumors; Oncotype DX testing has not been validated for any of these.

In short, the all-important management changes were not based, in large part, on things that gene-expression signature tests cover.

The editorialists concur that this review work is mainly the stuff of pathologists. "Clearly...use of such testing [Oncotype DX] is not enough," they write.

Why not perform a second pathology look for all breast cancer patients? "Clearly this is not possible, given the number of patients, specimens, slides, and available specialized breast pathologists. As the study by Kennecke et al shows, some sort of selection of cases is possible and needed," they write.