Skip to main content
Premium Trial:

Request an Annual Quote

Perlegen to Develop Dx to Predict Breast Cancer Risk Following HRT

Premium
Using a proprietary resequencing approach, Perlegen intends to develop a diagnostic test with internally identified genetic variants that will identify women at high risk for developing breast cancer following hormone replacement therapy. 
 
Perlegen announced last week that it is currently planning a study investigating this indication utilizing data from the Women’s Health Initiative – a large national study focused on prevention strategies for heart disease, breast and colorectal cancer, and fracture in postmenopausal women. From WHI’s databases – which includes information on more than 161,000 women across the country between ages 50 and 79 – Perlegen will gather clinical information on “thousands of women” who took estrogen and progestin and subsequently developed breast cancer.
 
“If this study successfully identifies rare genetic variants associated with greater risk of breast cancer development among women taking specific HRT, we plan to develop a test that can identify this variant in individual women to help them make decisions about HRT,” Perlegen CEO Bryan Walser told Pharmacogenomics Reporter this week.
 
The study is slated to end in early 2009, and will employ a proprietary resequencing approach that targets proteins and processes samples on an undisclosed second-generation sequencing platform.
 
The company noted in a statement that this new approach will enable it “to efficiently identify more of the genetic basis behind the differences in patients’ disease risks and response to drugs.” Perlegen’s study will only look at breast cancer risk, not at drug response, Walser noted.
 
Perlegen said its new sequencing approach is better than genotyping methods at gauging rarer SNPs. The method “targets the sections of the genome that are expressed as proteins, since even with fast, second-generation sequencing, addressing the entire genome in hundreds of cases and controls remains prohibitively expensive,” the company said in a statement.
 
Walser did not elaborate on the specifics of the company’s approach.
 
The fact that Perlegen is applying this sequencing technology to identify rare genetic variants in data subsets from WHI is noteworthy. In 2002, a large, randomized clinical trial looking at estrogen and progestin use in postmenopausal women enrolled in the WHI had to be halted when researchers observed that women who received hormones had an increased risk of developing breast cancer and heart disease.
 

“For a woman who has some identified risk factors for breast cancer … this additional information could be extremely valuable.”

Two years later, the first randomized clinical trial examining the effect of HRT use in women with recurrent breast cancer was published in The Lancet, more or less confirming WHI’s observations. In the study of 434 Scandinavian women previously diagnosed with breast cancer, women who received HRT to relieve the symptoms of menopause had more than three times as many breast cancer recurrences as those who did not take HRT.
 
Although the study was supposed to follow participants for five years, based on these findings, the researchers at the University Hospital in Uppsala, Sweden, cut short the study after two years, concluding that even short-term use of HRT posed an “unacceptably high risk” of breast cancer recurrence.
 
Since the study, which was not blinded or placebo-controlled, was stopped early, it recruited only 434 of 1,300 planned participants. As a result, “this study would not be strong enough to provide conclusive evidence that breast cancer survivors should avoid HRT,” JoAnne Zujewski, a medical oncologist who specializes in breast cancer at the National Institutes of Health Clinical Center, states on the National Cancer Institute’s website.
 
But Zujewski also notes that since the results from the Lancet study are consistent with the WHI findings, “as a practical matter, given what we already know about the serious risks and extremely limited benefits of HRT, these findings can be considered definitive.”
 
The US Food and Drug Administration recommends that women discuss with their doctors the risks and benefits of taking estrogen and progestin. If a physician feels that the benefits of HRT outweigh the risks, then the agency recommends that the hormones be taken "at the lowest doses for the shortest duration to reach treatment goals.”
 
Ultimately, a genetic test could help doctors more definitively determine whether a woman has an increased genetic risk for breast cancer, and as such, whether she should receive HRT.
 
“This new information will build upon our earlier work in common variants for breast cancer to allow physicians and patients to make better-informed choices about treatment options based on information associated with the individual’s particular genetics, enabling medicine that’s truly tailored to each individual,” Walser said in a statement.
 
“For a woman who has some identified risk factors for breast cancer, such as immediate family history, and is considering hormone replacement therapy to ameliorate the symptoms of menopause, this additional information could be extremely valuable,” he added.
 
The company said it plans to apply its new sequencing technology to identify genetic markers in other disease indications. Walser did not elaborate on this point.
 
Perlegen said last year that it was studying genetic risk factors for heart failure associated with two popular insulin-sensitizing thiazolidinediones: GlaxoSmithKline’s Avandia and Takeda’s Actos. The company has hinted that depending on the results it may develop a diagnostic test for the indication [see PGx Reporter 07-11-2007].
 
Also, earlier this year, Perlegen said it had obtained access to clinical treatment and outcomes data through a partnership with an undisclosed electronic medical-records provider.
 
Perlegen intends to mine these databases to identify genetic markers and develop diagnostic tests that can help personalize treatments for common conditions, such as heart attack, hepatitis C, breast cancer, and nicotine addiction [see PGx Reporter 04-02-2008].

Filed under

The Scan

Push Toward Approval

The Wall Street Journal reports the US Food and Drug Administration is under pressure to grant full approval to SARS-CoV-2 vaccines.

Deer Exposure

About 40 percent of deer in a handful of US states carry antibodies to SARS-CoV-2, according to Nature News.

Millions But Not Enough

NPR reports the US is set to send 110 million SARS-CoV-2 vaccine doses abroad, but that billions are needed.

PNAS Papers on CRISPR-Edited Cancer Models, Multiple Sclerosis Neuroinflammation, Parasitic Wasps

In PNAS this week: gene-editing approach for developing cancer models, role of extracellular proteins in multiple sclerosis, and more.