Breast cancer is diagnosed in over 200,000 women annually in the US, according to the CDC. The importance of detecting breast cancer early can’t be overstated: 1 out of 8 invasive breast cancers are found in women younger than 45, while about 2 of 3 invasive breast cancers are found in women age 55 or older. Furthermore, breast cancer in younger women is usually more aggressive. However, treated in the early stages it can be curable. Additionally, breast cancer in younger women is a growing problem. A recent article in the Journal of the American Medical Association revealed that the rate of metastatic breast cancer in American women 25 to 39 years old had nearly doubled over the past 35 years. This rate is much higher than expected by chance and, although unexplained, foreshadows a need for earlier diagnosis in this age group. Atossa Genetics, based out of Seattle, Washington, is attempting to address this trend. According to a recent press release:
In January, Atossa launched a new diagnostic test, named ForeCYTE, across the United States that can spot the very first signs of the cellular abnormalities that can lead to cancer. By itself, the test can reduce, or even eliminate, the need for most of today’s routine mammograms, MRIs and painful biopsies, dramatically improving doctors’ ability to spot telltale signs of potential cancer.
The test is based on harvesting tiny amounts of fluid from milk ducts in female breasts that previously were too small to be collected. The test has been shown to detect atypia with as few as 10 abnormal cells, enabling earlier intervention than with previous technology.
We had a chance to speak with Atossa’s CEO Steven Quay, MD PhD, about the ForeCYTE product and its potential in detecting breast cancer in younger women:
Ravi Parikh, Medgadget: Could you first give us a bit of your background? How did you get involved in cancer diagnostics?
Dr. Steven Quay, Atossa Genetics: Before I went into the biotechnology industry, I was on the faculty at Stanford, teaching and doing research on basic science. In the 80s, I invented the use of gadolinium for MRI, a way of looking for breast cancer that provides the best imaging tool, much better than mammography or ultrasound, although it is a bit expensive and can’t distinguish a benign from a malignant growth. I also founded another company in cancer therapeutics called Marina Biotech, which was developing RNA-based drugs. In fact, I have invented five FDA approved drugs, one FDA-cleared medical device, and five companies before Atossa Genetics.
So I’ve been thinking for a long time about cancer and how it is diagnosed and treated. About 14 years ago, I realized that the pathway to breast cancer is a lot like that of cervical cancer. Thanks to the Pap smear, which looks for pre-cancerous, abnormal cells in vaginal fluid taken from around the cervix, we know that cells don’t suddenly switch from normal to cancerous. They first go through a stage where they grow too fast and pile up on each other—called hyperplasia. Then the cells start to look funny, with abnormally large nuclei. That’s called atypical hyperplasia. Next, they turn cancerous, but without invading the surrounding tissue, a stage called carcinoma in situ. Finally, they start to spread. The whole process takes about 10 years.
At the early stages, the pathway to cancer can be reversed or blocked by treatment. That’s how the Pap smear—and its ability to detect these abnormal cells—has reduced the incidence of cervical cancer over 75%.
So I was excited to learn that the creator of the Pap smear, a Greek-born doctor named Georgios Nikolaou Papanikolaou, believed that the same kind of detection and treatment—and thus prevention—was possible with breast cancer. In fact, he was able to collect fluid leaking from women’s breasts and showed that this fluid contained cells that could be analyzed to detect the same cellular progression to cancer.
The problem that Papanikolaou had was getting enough fluid from the breasts of women to look for evidence of abnormal cells. That’s the problem that I’ve spent the last 14 years solving.
Medgadget: Tell us about the breast cancer diagnostics space before ForeCYTE. What was lacking from other tests in this space?
Quay: Think about how we detect breast cancer now. The two main methods are mammograms and self-examination. In the U.S., we now do about 39 million mammograms a year.
Both have serious drawback. A tumor that’s large enough to show up on a mammogram or to be felt as a lump already contains more than 100 million cancer cells. That’s pretty late to be detecting cancer.
Equally problematic, mammograms and self-exams will turn up many things that may look suspicious at first but turn out to be benign—so-called false positives. The only way to find out for sure is to plunge a needle into the breast to extract some of the cells. In the U.S., doctors perform about 1.2 million biopsies a year. Less than 10 percent of those biopsies detect cancer.
As a result, hundreds of thousands of women every year are faced with the fear that they might have cancer based on a suspicious mammogram. They worry for weeks about whether or not a devastating diagnosis is coming. That’s why mammograms have become so controversial. Some experts believe that the worry and suffering they cause isn’t worth the relatively low rate of successful cancer detection for many women. A study that came out in the New England Journal of Medicine just this past November found, for instance, that a million women may have been diagnosed with breast cancer, putting them through the anguish of a breast cancer diagnosis and debilitating treatment, even though the type of cancer didn’t really threaten their health or lives.
It was so clear to me that we need a test for breast cancer like the Pap smear that can reliably detect the first signs of cellular abnormalities—long before those cells turn into cancer and grow into tumors large enough to show up on mammograms. The test should also be able to determine the exact stage and severity of the pre-cancer or cancer.
Such a test would offer a far more accurate assessment of a woman’s risk of breast cancer, by combining the results of the cell analysis with family history and other factors. Most women will be at low risk, freeing them from the worry that breast cancer might strike. Even if abnormalities are detected, steps can be taken (from treatment with drugs to preventive mastectomies) that will keep cancer from ever developing in the first place.
Medgadget: How does ForeCYTE improve upon these previous models?
Quay: The key is early detection, not just of cancer cells, but also of the cellular precursors of cancer. The ForeCYTE test can spot as few as 10 abnormal cells, in contrast to the one billion cancer cells that must, typically, be present to show up on a mammogram. That not only offers a precise assessment of a woman’s risk of breast cancer, it also opens the door to prevention.
Medgadget: What is the procedure by which ForeCYTE collects early precursor cells for breast cancer?
Quay: As I mentioned, Dr. Papanikolaou realized decades ago that visible fluid leaks out of the nipples of some women. He was also able to use a breast pump-like suction device to extract fluid from others. The problem has long been that there isn’t very much of this fluid. Dr. Papanikolaou tried to get a drop that he could collect with a pipette.
In solving this problem, my first Eureka moment was realizing that it’s not necessary to collect a whole drop. My idea was to put a microfiber filter over the nipple that could absorb tiny amounts of fluid. To imagine how little fluid we get, it would take thousands of women to collect the same amount of fluid as in one human tear.
My second Eureka moment was figuring out that we could analyze the cells right on the filter.
It’s also important to understand why collecting the fluid is so essential. Just as vaginal fluid contains cells from the surface of the cervix (which is why the Pap smear works), the fluid from the breast contains cells from the linings of the ducts within the breast. These duct cells are responsible for about 90% of all breast cancers. Collecting the fluid and the cells it contains, therefore, is vital for spotting any cellular abnormalities on the path to cancer.
Medgadget: A major concern for breast cancer diagnosis has been false positive tests. How does your diagnostic differentiate between benign, in situ, and invasive cancers?
Quay: Mammograms have a high false positive rate because they can only spot lumps and other suspicious structures in the breast using physics. In order to know what those lumps are, it’s necessary to actually collect cells with a needle biopsy and examine them under a microscope to understand their biology.
Our test is like a non-invasive biopsy. It collects the cells directly. That makes it possible to determine the exact stage along the pathway to cancer, from the initial hyperplasia to actual cancer.
But we don’t just look at the cells. Our system also analyzes the pattern of gene expression in cells. Since gene expression changes as cells become cancerous, this pattern of gene expression offers another window into the precise stage.
Medgadget: Cancer is often harder to detect via mammogram in women with dense breast tissue. What impact can ForeCYTE have on these women?
Quay: That’s correct. The American Cancer Society warns women that dense breasts make it hard to spot cancer on mammograms, and five states—California, Texas, New York, Connecticut and Virginia—have passed legislation requiring that women whose mammograms show dense breasts must be notified of this fact. Several other states and the U.S. Congress are considering such legislation.
I’d like to point you to a study at the University of California, San Francisco. Researchers examined fluid from the breasts of 2,700 women between the ages of 25 to 65. The scientists found that women with dense breasts were more than four times more likely than women without dense breasts to have cells with atypical hyperplasia in the fluid collected.
That’s why it’s so crucial to actually collect cells from women with dense breasts, rather than relying on mammograms. We really need to understand the limits of mammography and give women a better test—one that is capable of detecting the earliest signs of pre-cancer.
Medgadget: Where do you see ForeCYTE fitting into the timeline of breast cancer management currently in place? Do you see it as an adjunct or substitute to traditional methods of diagnosis, such as invasive biopsy or mammography?
Quay: There is already a huge industry based on mammograms. In my heart, I truly believe that our test will eventually replace mammography and invasive biopsies. But given the enormous entrenched interests and the skepticism about anything new, I think that our test will begin as an adjunct method of diagnosis. Doctors can more clearly see the benefits in, say, women with dense breasts, or as a way to help figure out what a suspicious mammogram might mean.
As the medical community becomes more familiar with the approach and its advantages, then I can see it gradually becoming the standard of care. Another benefit is that our test can save the health care system, which now spends tens of billions of dollars a year on breast cancer diagnosis and treatment, a huge sum of money.
Medgadget: ForeCYTE is often compared to a Pap smear in your press releases. What are the similarities and differences between the two tests in terms of accuracy and ease of use?
Quay: They are very similar. Both are designed to find pre-cancer not really cancer. Both offer a way to directly collect the cells of interest. Both examine the cells to determine the exact stage using well-established pathology methods. And both offer the opportunity for early treatment that can prevent the cancer.
Medgadget: You launched ForeCYTE earlier this year. In your previous trials, what have clinicians been saying about it?
Quay: We have been very gratified with the experiences of doctors who are using this approach. Dr. John Tedeschi, a solo practitioner in Robbinsville, New Jersey, tells the story of a recent patient who had a completely normal mammogram. But her breast duct fluid contained abnormal cells. Dr. Tedeschi suspected—and tests confirmed—that she had cancer in situ.
The early detection allowed the cancer to be completely eliminated before it could invade the surrounding breast tissue or spread more widely. The woman had a mastectomy and “was completely cured,” Dr. Tedeschi told one of my colleagues. “It was phenomenal. We detected the cancer five years before it would have shown up on a mammogram.”
Medgadget: What can you tell us about future diagnostics or other products coming out of Atossa Genetics?
Quay: One of the most exciting recent studies is the treatment of seventeen women, who had been diagnosed with cancerous lumps, with chemotherapy infused through their ducts with a micro-catheter. Because the drug went directly into the breast duct (not the bloodstream), levels of the drug were 50 times higher in the breast, but 50 times lower in the bloodstream, than with conventional IV chemotherapy. The result: Far higher effectiveness and virtually no side effects. When the women had surgery two weeks later, as scheduled, their tumors were already dead in all cases.
That study points to a potential revolution in cancer treatment. If the ForeCYTE test detects abnormal calls, it should be possible to treat the ducts from which the cells came to reverse or eliminate the abnormalities. So just as with the Pap smear and cervical cancer, we should be able to prevent the disease altogether in a high percentage of women. We plan to conduct clinical trials to prove that this can be done.
We also are developing two important tests for women with existing cancer: the NextCYTE Breast Cancer Test, which examines all 22,000 active genes in a surgical biopsy specimen of cancer and predicts treatment response and five-year survival, and the ArgusCYTE Breast Health Test, a blood test for the 2.5 million breast cancer survivors, which looks for rare, circulating tumor cells that are appear up to two years before a recurrence. We hope to introduce these tests sometime this year.
Medgadget: Anything else you would like to add?
Quay: I’m tired of women dying of breast cancer. I’ve been working for years to reduce the toll of pain, suffering and premature death. And with the ForeCYTE test, we finally have the approach we need to make a real difference.
ForeCYTE is a revolutionary tool and has the potential to disrupt the breast cancer diagnostics market. We look forward to hearing more about it, NextCYTE, and ArgusCYTE as the year progresses.
Check out a video of How ForeCYTE works:
Product Page: ForeCYTE…
