On 2014 Nov 20, Neven Patrick commented:

Although results from ongoing prospective trials looking into the predictive value of multigene signatures (MGS) for chemotherapy benefit are pending, many use them for prognostic purposes. In general, this leads to less adjuvant chemotherapy. This paper reported on how a multidisciplinary team (MDT) changed treatment decisions studying 75 patients with a grade 1-2 cT1-2N0 ER-positive, HER2-negative breast cancer. Clinical risk by MDT based on (St Gallen criteria) pathological tumor size, grade, nodal stage, steroid receptors and Ki-67 was compared with MammaPrint® (MP) risk. There was discordance between clinical and MP-risk in 29 out of 75 patients; 21 had a clinical high, MP low and 8 a clinical low, MP high risk. In this group of 29, 4 out of 8 with a clinical low, MP high risk did and 10 out of 21 in the clinical high, MP low risk did not get chemotherapy. All together, based on clinical risk alone, 31 of 75 women would have received adjuvant chemotherapy while this changed to 25 of 75 when incorporating the MP-risk. The use of MGS in this cohort was cost effective. The paper however, lacks some important details that are relevant and will help understand the use of MGS in this MDT. First, the discordance rates between clinical and MGS-risk in this paper are much higher for the clinical high risk patients (67%)compared with other experiences with MGS, like MP in RASTER or MINDACT (Bueno-de-Mesquita et al., 2007; Rutgers et al., 2011). This might be related to an overestimation of the clinical or underestimation of the MGS-risk. The definition they used for clinical risk is lacking and suggests an overestimation of clinical risk as 41% of women with a low to intermediate risk were stratified by the MDT as high risk. Otherwise, MGS might underestimate relapse risk. It would be interesting to know from the patients’ demographics whether some of the patients stopped exogenous hormones prior to breast cancer surgery. Short term changes in the hormonal environment following an ER-positive breast cancer diagnosis on core needle biopsy might confound MGS results. This has been shown for proliferation markers other than MGS for example with hormone replacement therapy withdrawal. Second, the authors state why they decided to give adjuvant chemotherapy in 11 out of 21 women with a clinical high, MP low risk, but they did not indicate why adjuvant chemotherapy was or was not given to half of the patients with a clinical low, MP high risk.

On 2014 Nov 20, Neven Patrick commented:

Although results from ongoing prospective trials looking into the predictive value of multigene signatures (MGS) for chemotherapy benefit are pending, many use them for prognostic purposes. In general, this leads to less adjuvant chemotherapy. This paper reported on how a multidisciplinary team (MDT) changed treatment decisions studying 75 patients with a grade 1-2 cT1-2N0 ER-positive, HER2-negative breast cancer. Clinical risk by MDT based on (St Gallen criteria) pathological tumor size, grade, nodal stage, steroid receptors and Ki-67 was compared with MammaPrint® (MP) risk. There was discordance between clinical and MP-risk in 29 out of 75 patients; 21 had a clinical high, MP low and 8 a clinical low, MP high risk. In this group of 29, 4 out of 8 with a clinical low, MP high risk did and 10 out of 21 in the clinical high, MP low risk did not get chemotherapy. All together, based on clinical risk alone, 31 of 75 women would have received adjuvant chemotherapy while this changed to 25 of 75 when incorporating the MP-risk. The use of MGS in this cohort was cost effective. The paper however, lacks some important details that are relevant and will help understand the use of MGS in this MDT. First, the discordance rates between clinical and MGS-risk in this paper are much higher for the clinical high risk patients (67%)compared with other experiences with MGS, like MP in RASTER or MINDACT (Bueno-de-Mesquita et al., 2007; Rutgers et al., 2011). This might be related to an overestimation of the clinical or underestimation of the MGS-risk. The definition they used for clinical risk is lacking and suggests an overestimation of clinical risk as 41% of women with a low to intermediate risk were stratified by the MDT as high risk. Otherwise, MGS might underestimate relapse risk. It would be interesting to know from the patients’ demographics whether some of the patients stopped exogenous hormones prior to breast cancer surgery. Short term changes in the hormonal environment following an ER-positive breast cancer diagnosis on core needle biopsy might confound MGS results. This has been shown for proliferation markers other than MGS for example with hormone replacement therapy withdrawal. Second, the authors state why they decided to give adjuvant chemotherapy in 11 out of 21 women with a clinical high, MP low risk, but they did not indicate why adjuvant chemotherapy was or was not given to half of the patients with a clinical low, MP high risk.