MammaPrint Shows Which Breast Cancer Patients Can Skip Chemo

Fallleaves

'When the MINDACT trial began in 2007, it recruited patients with early-stage breast cancer and negative lymph nodes, but the protocol was changed in 2009 to also allow patients with one to three positive nodes, Dr Piccart noted. In the overall trial population, about one in five patients had node-positive disease, she noted, and about 10% of tumors were HER2-positive, which are biologically aggressive.

The genomic test was compared with clinical assessment using Adjuvant! Online, and women were classed into one of four categories.

Women who were assessed as low risk by both genomic and clinical tests — i.e., G-low, C-Low (n = 2743; 41%) — did not received chemotherapy, and the results show that they had the best outcomes, with a distant-metastasis-free survival at 5 years of 97.6%.

Women who were assessed as high risk by both measures — i.e., G-high and C-high (n = 1807; 27%) — were strongly encouraged to have chemotherapy, but despite this, they had the worst outcomes, with a distant-metastasis-free survival rate at 5 years of 90.6%.

The main part of the trial focused on the women in which the results were discordant, having been assessed as high risk by one measure but low risk by the other, and these patients were randomized to receive chemotherapy or not (anthracycline or taxane regimens). Patients also received endocrine therapy (tamoxifen for 2 years followed by letrozole for 5 years or letrozole for 7 years).

The outcomes in these two discordant groups were similar, with a distant-metastasis-free survival rate at 5 years of 94.8% in women assessed as C-high, G low (n = 1550; 23%), and a rate of 95.1% in women assessed as C-low, G-high (n = 592; 9%).

The curves for patients who did receive chemotherapy were almost superimposable on those who did not, Dr Piccart said, suggesting that there was no benefit from the chemotherapy.

"We know that not all patients who currently receive adjuvant chemotherapy need the treatment, and they endure significant adverse side effects without gaining clinical benefits," Dr Piccart commented. These new results show that use of this genomic assay helps to identify those patients that can skip chemotherapy, even if they are assessed clinically as being high risk.'

http://www.medscape.com/viewarticle/862194#vp_2

To me the take-away is that Mammaprint IN CONJUNCTION WITH clinical assessment can more clearly identify who can skip chemo. The crux is the cases where Mammaprint and clinical assessment are in disagreement. Mammaprint doesn't always get it right there by itself, either. There were 9% of cases where if you relied on Mammaprint alone, chemo would be recommended, but wouldn't be necessary. So the question is: what are the clinical factors that trump the genomic flags, and vice versa?

BarredOwl

Hi Fallleaves:

Thanks for posting. This article includes the text of the AACR abstract:

http://www.eortc.org/news/mindact-mammaprint-genet...

From the abstract, it looks like they used some kind of "modified version Adjuvant! Online" to assess clinical risk. I am not sure whether the tool was specially modified for the purposes of the clinical trial or if the modified version used is already publicly available.

BarredOwl

solfeo

Adjuvant! Online has been down for updating as long as I have been looking since diagnosis, and a recent announcement on the site said it is taking longer than they expected to finish. There is CancerMath but it calculates mortality risk and not risk of metastasis-free survival.

Does anyone know if there is another alternative that might substitute for Adjuvant! Online?

besa

http://www.medpagetoday.com/MeetingCoverage/AACR/5...

Another link to an abstract about the study.

barcelonagirl

Here's another link to the MINDACT study:

http://www.onclive.com/conference-coverage/AACR-20...

BarredOwl

Hi:

Version 2.2016 of the NCCN guidelines for Breast Cancer has recently been issued with updated charts, Discussion and bibliography, and can be accessed for free with registration here:

NCCN Guidelines: https://www.nccn.org/store/login/login.aspx?ReturnURL=https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf

The basic recommendations regarding OncotypeDX for invasive disease and other tests (e.g., MammaPrint (aka "70-gene signature")) in chart BINV-6 (at .pdf page 18) are unchanged at this time. Perhaps the committee is awaiting a full-length publication. However, the 2016 AACR abstract discussed above has been added to the updated bibliography, and the following text has been added to the Discussion ([text added by me]):

"The MINDACT trial is [a] phase III trial comparing the 70-gene signature [MammaPrint] with the commonly used clinicopathologic criteria in selecting patients for adjuvant chemotherapy in breast cancer with 0 to 3 positive nodes.(292) The early results from the MINDACT trial suggest that the 70-gene signature can help avoid chemotherapy in certain patients regardless of larger tumor size and nodal status, without compromising the outcome.(293) Among the MINDACT trial patients, if [the] decision on administering adjuvant chemotherapy was based on clinical characteristics alone (tumor size and nodal status), 50% would receive adjuvant chemotherapy; however, only 36% received chemotherapy using the risk status based on the 70-gene signature—an absolute reduction of 14% in chemotherapy administration rate.(293)

Reference 293. Piccart M, Rutgers E, van' t Veer L, et al. Primary analysis of the EORTC 10041/ BIG 3-04 MINDACT study: a prospective, randomized study evaluating the clinical utility of the 70-gene signature (MammaPrint) combined with common clinical-pathological criteria for selection of patients for adjuvant chemotherapy in breast cancer with 0 to 3 positive nodes [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, Louisiana: AACR; 2016. Abstract CT039 2016.

BarredOwl