Key Factor Missing From Prognostic Breast Cancer Models

Affects Who Receives Chemotherapy

Nick Mulcahy

December 11, 2010

December 11, 2010 (San Antonio, Texas) — Palpability is prognostic in women with grade 2 breast cancer and should be added to commercial prognostic tests such as the Oncotype DX (Genomic Health) and Adjuvant! Online (Adjuvant! Inc), concludes a new study from Belgian researchers.

The study of 1000 women with primary operable grade 2 breast cancers shows that in a univariable analysis, palpable breast cancers had a worse prognosis than nonpalpable cases (hazard ratio [HR], 1.96; 95% confidence interval [CI], 1.13 - 3.71). The prognostic effect of palpability remained when the investigators did a multivariate analysis (HR, 1.76; 95% CI, 0.92 - 3.57).

The median follow-up in the study was 80 months.

Another variable in the study that was a somewhat comparable hazard to palpability was having more than 4 positive lymph nodes (HR, 2.52; 95% CI, 1.26 - 4.82)

"Palpability should be added to prognostic models," said study senior author Patrick Neven, MD, from University Hospitals Leuven, in Belgium, adding that "mode of detection" (self- vs screen-detected) was also important. In the study, the screen-detected cancers showed better prognosis (HR, 0.63; 95% CI, 0.42 - 0.93) than self-detected cancers in the univariable analysis.

Dr. Neven spoke to Medscape Medical News at a poster session here at the 33rd Annual San Antonio Breast Cancer Symposium, where he presented his new study.

Another clinician and meeting attendee agreed with Dr. Neven's evaluation of palpability and explained the logic behind the importance of mode of detection: "If you are going to do a mammogram every year, you will preferentially pick up slowing growing tumors. The tumors that show up in between mammograms are quicker-growing, more aggressive, and will do worse," said Steven Vogl, MD, suggesting that those latter tumors are also more likely to be self-detected and palpable. Dr. Vogl is a community-based clinician from the Bronx, New York.

The study findings have important ramifications for treatment, said Dr. Neven.

"If you have patients with screen-detected, nonpalpable tumors — which is about 20% of all grade 2 breast cancers — you should not add chemotherapy to treatment," he said.

The reason for the decision is that in the new study, only 2.3% of these women with screen-detected and nonpalpable tumors had metastatic relapse at 80 months. Therefore, the majority of these women do well without chemotherapy, and only a very few relapse metastatically. In those cases, the tumor is so aggressive that chemotherapy may not help much, Dr. Neven said.

Dr. Neven noted that only about 20% of all the women in the new study received chemotherapy. He said that in the United States, in this same patient population, about 40% of the women would have received chemotherapy. Americans' inclination to prescribe chemotherapy is partly a result of their use of commercial prognostic tools, suggested Dr. Neven.

Nearly All Self-Detected Cancers Were Palpable

In the study, the investigators used data from 1000 women with newly diagnosed and operable breast cancer who were seen at the University Hospitals Leuven. There were 397 women with screen-detected tumors; of those, 227 were palpable and 170 were nonpalpable. There were also 602 self-detected tumors; predictably, most were palpable (582), and very few were nonpalpable (20).

The average age for all of the women in the study was about 57 years, with the exception of the women with self-detected, nonpalpable tumors, who were much younger and had a median age of 47 years.

The women with palpable, self-detected tumors were more likely to have lymph node involvement and bigger tumors, as well as more aggressive treatment. They were also more likely to have a metastatic event (9.9%) than women with screen-detected, palpable tumors (5.3%).

Women whose tumors were nonpalpable had lower incidences of metastatic events: 2.3% for those nonpalpable and screen-detected tumors and 0% of the nonpalpable, self-detected tumors.

The women with palpable, screen-detected tumors had more local/contralateral events than their self-detected counterparts: 5.7% vs 3.7%.

In terms of the prognostic variables, the researchers looked at age at diagnosis, tumor size, screening, palpability, lobular type, adjuvant chemotherapy, and/or endocrine therapy. (More than 90% of all of the women were estrogen-receptor positive and received hormonal therapy.)

The authors have disclosed no relevant financial relationships.

33rd Annual San Antonio Breast Cancer Symposium: Abstract P4-08-09. Presented December 11, 2010.

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