A study published online in the August 2014 edition of the Annals of Surgical Oncology shows that BluePrint (Agendia Inc) proves to be superior to conventional subtyping for analyzing breast cancer before surgery. [1] The study, which will also be published in the October print edition of the journal, is part of the ongoing Neoadjuvant Breast Registry Symphony Trial (NBRST, pronounced “N-breast”).[2][3]
These finding may eventually change the way physicians evaluate and treat breast cancer. The researchers concluded that the BluePrint genomic test provides more accurate information about the molecular subtype of a specific breast cancer, compared to the use of conventional immunohistochemistry (IHC)-fluorescence in situ hybridization (FISH) pathology tests.
This genomic test gives us a better picture of which patients will and won’t respond to preoperative therapy, and also helps suggest the best course for therapy…
Observational study
The prospective observational study of 426 patients was recently published online by the Annals of Surgical Oncology. The study showed that 37 of 211 (18%) IHC-FISH hormone receptor (HR)+/HER2-patients were reclassified by BluePrint as Basal (n=35) o HER2 (n=2).
The study further showed:
- Fifty-three of 123 (43%) IHC/FISH HER2+ patients were reclassified as Luminal (n=36) or Basal (n=17);
- Four of 92 (4%) IHC/FISH triple-negative (TN) patients were reclassified as Luminal (n=2) or HER2 (n=2);
- NCT pCR rates were 2% in Luminal A and 7% Luminal B patients versus 10% pCR in IHC/FISH HR+/HER2- patients;
- The pathological complete response (pCR) rate for the neoadjuvant chemotherapy (NCT) was 53% in BluePrint HER2 patients. This is significantly superior (p=0.047) to the pCR rate in IHC/FISH HER2+ patients (38%). The pCR rate of 36 of 75 IHC/FISH HER2+/HR+ patients reclassified as BPLuminal is 3%. NCT pCR for BluePrintBasal patients was 49 of 140 (35%), comparable to the 34 of 92 pCR rate (37%) in IHC/FISH TN patients.
As a result, the researchers concluded that the BluePrint assay may be a better guide than IHC-FISH tests in making decisions about how to treat early-stage breast cancer before surgery.
Researchers also reported that the 80-gene BluePrint test reclassified 22% of tumors overall — more accurately identifying breast cancer subtypes than could be done with IHC-FISH testing. “This genomic test gives us a better picture of which patients will and won’t respond to preoperative therapy, and also helps suggest the best course for therapy,” said Pat Whitworth, MD., a Nashville surgical oncologist and lead author of the article.
The BluePrint test is performed in conjunction with Agendia’s 70-gene MammaPrint test. MammaPrint provides the foundational risk classification of High Risk or Low Risk about breast cancer recurrence, without the ambiguity of intermediate results. Additional therapy-predictive information is then conferred by the 80-gene BluePrint assay, which identifies the molecular subtype. “One implication of the study findings is that we will eventually end up evaluating and treating many breast cancer patients differently than we do now, because we will rely on their molecular subtype rather than just IHC-FISH pathology results,” Whitworth noted.
A substantial shift
The findings may result in a substantial shift in how breast cancer is analyzed and treated. “Physicians have for nearly 40 years looked to the predictive capabilities of pathology tests such as IHC and FISH to generate clinical decisions,” Neil Barth, MD., an oncologist and Agendia’s Chief Medical Officer noted. “But we have also recognized these pathology tests are not complete, as we have often seen discordance between what we were told by IHC-FISH and how the cancer actually behaved.”
Improved understanding
Barth explained that the new study, combined with other recent research, “…is telling us that we now have a better tool to measure the dominant biological drivers of each individual breast cancer.” He likened this “next iterative step” in understanding breast cancer to moving from having a cell phone to having a smart phone.
“With molecular subtyping, we now have something akin to a smart phone’s GPS, to help us better determine where we are and where we can go,” Barth said.
The new study also confirmed previously published research by Stefan Gluck, MD., that preoperative chemotherapy given to patients with the common Luminal A subtype of cancer generally has little benefit. “The BluePrint test takes a much more nuanced look at breast cancer biology than is available from IHC-FISH tests,” Whitworth explained. “This new information about luminal cancers is one example of how molecular subtyping may help guide preoperative treatment decisions.”
Triple positive beast cancer
Whitworth said that research into molecular subtypes, if confirmed by other research, may also change the treatment of “triple positive” breast cancers – those that are reported as HER2, ER and PR positive by IHC-FISH testing. “According to this new research, about half of these patients do not exhibit HER 2-type responses, and may therefore respond better to a different treatment than would be given to a HER2-positive patient,” he said.
Potential benefits
The potential benefits of neoadjuvant cancer treatment are emphasized by the American College of Surgeons Commission on Cancer. On According to the commission’s public statements, many people are not provided the advantages of pre-surgical therapy despite its known advantages. According to the commission physicians and patients are advised not to use surgery as the initial treatment without considering pre-surgical (neoadjuvant) systemic and/or radiation for cancer types and stage where it is effective at improving local cancer control, quality of life or survival.
Patients talk
Kara Sanders was one of Whitworth’s patients in the Annals of Surgical Oncology study who, at the time of diagnosis, was a federal probation officer in her late thirties. She was among patients whose cancer was reclassified by MammaPrint and BluePrint, after it had been analyzed by IHC-FISH as being triple positive. Guided in part by the genomic tests, her neoadjuvant treatment was successful in achieving a pathologic complete response: the absence of invasive carcinoma in the breast and axilla prior to surgery.
“After my diagnosis I couldn’t find a lot of information about breast cancer in premeopausal women,” Sanders commented. “I was very happy to be part of the trial to contribute to the research, because it’s very empowering to have more knowledge of this kind.”
In addition to Whitworth’s Nashville Breast Center, the multi-site study drew patients from a broad base of community and academic practices, including hospitals in Washington, D.C., Dallas, Virginia, Pennsylvania and Georgia.
For
more information:
[1] Whitworth P, Stork-Sloots L, de Snoo FA, Richards P, Rotkis M, Beatty J, Mislowsky A, Pellicane JV, et al. Chemosensitivity Predicted by BluePrint 80-Gene Functional Subtype and MammaPrint in the Prospective Neoadjuvant Breast Registry Symphony Trial (NBRST). Ann Surg Oncol. 2014 Aug 7. [Article][PubMed]
[2] Whitworth PW, Gittleman M, Akbari S, Stork L, De Snoo F, Gibson J, Beitsch PD, er al. First results of the prospective Neoadjuvant Breast Registry Symphony Trial (NBRST).J Clin Oncol 31, 2013 (suppl; abstr e22117)[Abstract]
Clinical trials
[3] NBRST: Prospective Neo-adjuvant REGISTRY Trial – NCT01479101 [Study Record Detail]
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