A preview of ASCO – The new way of doing clinical trials

BY DEBU TRIPATHY | MAY 31, 2011

For decades, we have used the same system of testing and ultimately approving new treatments for cancer. The starting point of new drugs has become sexier--by targeting genetic lesions and avoiding some of the poisonous effects of older drugs. But the rest of the sequence of trials toward the road to approval is stale. It still starts by demonstrating safety (phase 1 trials), then some sense of effectiveness in shrinking tumors (phase 2) and ultimately a large trial comparing it with "standard" treatment or to adding the new drug to standard treatment (phase 3). Drug companies are focused on meeting the metrics by the FDA for approval--usually improving survival or time to recurrence or delaying progression. This used to mean showing a statistically significant improvement in a large number of eligible patients, even if the overall improvement was small--just a couple of months of extra survival.

This model is no longer working well because as we discover that cancer is broken down into small subsets that are biologically distinct, with only some subsets responding to targeted drugs. Given the side effects and spiraling costs of newer drugs, what might work for a cheaper and safer hypertension drug will certainly not apply for cancer therapies. Having to treat hundreds of patients for only a few to benefit is not sustainable, especially when newer technology is available to improve the situation. This year at ASCO, you will read our blogs about exciting updates on the cancer front, and a common theme will emerge. A much greater effort is being made to understand what subset of patients might respond even before a new agent is ready for human testing. Sometimes it is not clear what tissue tests should best qualify a clinical trial subject, so even in phase 1 testing, analysis of tissue is not built into the study in hopes of refining eligibility criteria for future trials.

Another innovative trial design we use when we do not know what patient population might best respond is called a "randomized discontinuation trial." It is based on the notion that only a small fraction of patients might respond. A large number of patients are initially tested (after basic safety is established). A very small number of patients might actually have shrinkage of tumor and they stay on treatment, while those who progress are taken off the study. However, those who have neither growth nor shrinkage after a defined period of time (termed "stable disease") are randomized to either continue or discontinue therapy. If those who stop therapy exhibit tumor growth after some time more so than those who continue, it proves that the drug is effective and may even shed some light on the tumor characteristics that predict response in the small fraction of cases. Of course, the trial can be designed to allow the "randomized discontinuation" group to restart therapy with the assumption that they might derive a benefit.

Another approach is called "adaptive trial design" where the results of the trial are analyzed in real time, and the randomization scheme (the fraction of patients randomized to standard vs. experiment treatment) changes over time to maximize the efficiency of the trial. While these ideas are not exactly new, they are being applied more often, especially for biologically targeted drugs since we have tools newly made available, such as rapid whole genome sequencing that can be feasibly done for at least part of the genome and are standardized to the point that they can be used for both pilot and large definitive trials. This will no doubt be a part of the major overhaul of the clinical research process currently under way in the government and drug industry sectors--the transformation of cancer clinical trials has just begun.

• Two new drugs approved, one pulled from the pipeline
• Cancer screening rates low
• A call for more pancreatic cancer research
• An introduction to cancer: From a father and his daughter
• The cushion of silence

Chemotherapy shortage: A symptom of a bigger problem

BY DEBU TRIPATHY | JANUARY 17, 2011

You may have heard about the chemotherapy shortage over the past few weeks whereby the supply of certain drugs is limited and even causing some infusion centers to reschedule appointments or change treatment plans.

While this is not a major disaster and will be fixed shortly, it is emblematic of our country's whole medical system. We really don't have a shortage of drugs as a looming problem – it is more a matter of supply temporarily not meeting demand due to production, transport and inventory. But the bigger problem is coordination. Because our health care is decentralized and insurance coverage is spotty, you will get a wide spectrum of opinions about our nation's health care – from "best in the world" to "bloated, expensive, inefficient and unfair."

I see incredible wastage of resources in my everyday practice of medicine – tests that are repeated because earlier results are unavailable or not felt to be reliable. Treatments or diagnostics that are "long shots" and made by both doctors and patients in haste without much reflection. State-of-the-art facilities and equipment that are not used to capacity.

There is much talk about electronic medical records (EMRs) as the savior for all of these problems, although the verdict so far is that these systems have not really made much of an impact on quality or efficiency of care. However, we are really only on "version 1.0" of EMRs, and further integration and standardization of these systems do hold the potential to improve many aspect of medical care, particularly the coordination of care and other activities (like chemotherapy availability) that are essential in the very complicated arena of cancer management. I believe that the public needs to be very engaged in the debate regarding EMRs and coordination of care because quality and affordability, especially in oncology, is at stake.

An informed and vocal public can steer the health care debate from the rancorous halls of Washington to a discourse with the public and ultimately the enactment and adoption of a coordinated information network, including patient portals and a seamless transfer of information across medical practices and hospitals. These advances have had huge effects in commerce, banking, entertainment and even social networking and dating, so why is medicine being left behind?

• Two new drugs approved, one pulled from the pipeline
• Cancer screening rates low
• A call for more pancreatic cancer research
• An introduction to cancer: From a father and his daughter
• The cushion of silence

Finding the Perfect Prevention Drug

BY DEBU TRIPATHY | NOVEMBER 30, 2010

Using drugs to prevent cancer has long been sought, as many clues from the laboratory and observational population studies have pointed to several clues and candidate drugs. Testing these in the clinic requires huge numbers of subjects (well over 10,000) that have to be randomized to placebo or the active drug and then followed for many years, an expense that few companies or the government will take on. The first prevention drug, tamoxifen was approved in 1998 to lower the risk of getting breast cancer (lowered the rate from about 2% to 1% over 5 years). However, this drug is rarely used, in part because of bothersome side effects, but also more serious ones like an elevated risk of uterine cancer and blood clots.

A cousin of tamoxifen, raloxifene (Evista), with a lower risk of both these side effects was approved in 2007. This class of drugs, known as selective estrogen receptor modulators (SERMs), also improves bone mineral density--Evista is actually approved for osteoporosis. Since the estrogen receptor pathway mediates many different physiological processes ranging from breast cancer to clotting to bone density, SERMs have been engineered, through slight chemical alterations in their structures, to be the perfect women's health drug--with the potential to lower cancer risk and to improve bone and cardiac health.

Evista was designed to not produce stimulation of uterine cells as to avoid a known complication of tamoxifen--an increased risk of uterine cancer. While it did achieve that goal, its breast cancer risk-attenuating activity is not as good as tamoxifen's, and it still raises the risk of blood clots. Another SERM called lasofoxifene has come a little closer, with a recent update of a large randomized trial now showing a lowering of breast cancer rates by nearly 80%--that is from 1 in every 114 women to 1 in every 550 women over 5 years. It also lowered the bone fracture rate and even the stroke rate without increasing endometrial cancer risk. However, it did increase blood clotting--the one SERM side effect that we cannot seem to "engineer out." Still, the FDA earlier rejected lasofoxifene as a preventive drug because the overall death rate (from non-cancer causes) was higher in the low-dose arm compared to placebo even though it was not in the high-dose arm. This turn of events reflects the frustration by all parties--doctors, patients, researchers and the FDA itself.

We have prevention drugs that can lower cancer risk with side effects that are much lower in number than the cancers prevented. So far, no drug is free of rare but serious side effects--and coupled with the less dangerous but still bothersome side effects, such as hot flashes and a myriad of less characterized symptoms, it is understandable why only a fraction of eligible patients opt for FDA-approved breast cancer prevention drugs. Also, there is no statistical difference in the overall death rate in prevention studies, in part because they were not designed to be large enough to detect them, but it may also be that we are preventing the less dangerous estrogen receptor-positive breast cancers.

The field of cancer prevention is still very active but could use a shot in the arm. While the science behind it is very elegant, it appears that, like many other things in life, it comes down to a popularity contest. Doctors and patients will vote with their feet--with prescribing and compliance hinging on both a better side effect profile, and a bigger impact on saving lives, not just lowering the number of cancer cases.

• Two new drugs approved, one pulled from the pipeline
• Cancer screening rates low
• A call for more pancreatic cancer research
• An introduction to cancer: From a father and his daughter
• The cushion of silence

Is a new anti-angiogenic strategy on the horizon?

BY DEBU TRIPATHY | OCTOBER 28, 2010

As both a clinician and scientist, I always look at new biological findings with a mixture of enthusiasm and skepticism. In the New England Journal of Medicine, a very provocative finding was published (the Journal prides itself on being the first to report something that just might be a game changer).

A new property of a well-known protein called the follicle stimulating hormone receptor (FSHR) was described – namely, its presence in the blood vessels of many different types of tumors in humans – breast, prostate, colon, and host of other cancers. Normally, FSHR is expressed in specific cells within the ovaries and testes, in keeping with its known roles in sex hormone production and menstrual cycle control. This was a very carefully done study, with multiple antibodies against FSHR and very careful analysis over the areas of many tumors and adjacent normal tissue. Staining for FSHR was seen in tumor-associated blood vessels within all of the tumor tissues in 1,336 cases, and in some cases of "precancerous" tissue. Its expression in blood vessels fell off progressively in moving away from the tumor into normal tissue.

Might this new finding represent a target for treatment against many types of cancer? Well, we have been down this road before – a tumor-specific antigen that is hailed as a way to develop the perfect magic bullet, only to lead to disappointment once tested in patients. Still, anti-angiogenic therapy - the targeting of tumor blood vessels that are necessary for tumor growth and spread, has been a successful strategy, with the drug Avastin showing improvements survival in colon and brain cancer, but not fully curative in advanced cancers.

In the case of breast cancer it delays progression without improving survival. Avastin does not only target tumor blood vessels, since the growth factor it targets is also involved in non-tumor blood vessel formation and other cellular functions – hence it has side effects.

In the case of FSHR, the investigators showed that they can deliver particles bound to antibody to tumor blood vessels using animal tumor models. This might therefore represent a promising therapeutic avenue, although there may be toxicity to the ovaries and testes that would need to be addressed. It remains unknown why FSHR is expressed on tumor blood vessels – but there is good reason why it made the "scientific front page."

• Two new drugs approved, one pulled from the pipeline
• Cancer screening rates low
• A call for more pancreatic cancer research
• An introduction to cancer: From a father and his daughter
• The cushion of silence

The evolving story of estrogen replacement and its effects

BY DEBU TRIPATHY | APRIL 17, 2010

As more and more information comes in from large-scale trials, it is clear that estrogen replacement therapy in the usual form of an estrogen plus a progesterone drug (E+P), commonly called hormone replacement therapy or HRT, increases the risk of breast cancer.

When the results from the "definitive" randomized trial, the Women's Health Initiative (WHI) study, were announced in 2002 and showed about 25 percent more breast cancers with E+P compared with placebo, the use of HRT plummeted. A few years later, this became evident with fewer breast cancers diagnosed, reversing a longstanding trend of rising rates.

However, the estrogen receptor is expressed in many other tissues besides the breast, so further analyses of this trial looking at other cancers showed interesting effects--such as a higher death rate from lung cancer with E+P, but interestingly, a lower risk of colorectal cancer.

Just this month, a group at the University of North Carolina, using a less reliable case-control design, found the lower end of colon and rectal cancer risk has halved with any HRT use. However, on further follow-up of the WHI study, it turns out that the colorectal cancer cases on E+P were of higher stage, so that there were actually more deaths from colorectal cancer on replacement therapy. Finally, E+P also increased the risk of stroke and blood clots in the lung and appeared to raise the chance of heart attacks, especially in the first year of therapy. It did lower hip fracture rates, in keeping with its bone density-enhancing properties.

So clearly, E+P causes more cancers and does not, as initially thought, protect the heart. Even though there are still detractors who criticize the trial design--the age at which patients were started on therapy and the exact form of therapy--one wonders if there is at all a silver lining in this story.

Well, there might be--and that is therapy with estrogen alone. This therapy can only be given to women who have had their uterus removed. In women who do have a uterus, estrogen-only therapy can cause a build-up of the uterine lining and raises the uterine cancer risk. (Women with a uterus receive E+P because adding progesterone reduces that risk of uterine cancer).

The WHI study also randomized more than 10,000 women who had prior hysterectomy and gave them either estrogen alone or placebo. In this trial there were actually fewer cases of breast cancer, not quite statistically significant, though. There was no effect on colorectal or lung cancers. There were also slightly fewer stokes and heart attacks, but more clots to the lung; however none of these were statistically different.

So, it is possible that estrogen might be a useful drug in women without a uterus, but clotting problems are still a concern. We have seen the emergence of designer anti-estrogen drugs like raloxifene (approved for breast cancer reduction and osteoporosis), and more recently lasofoxifene, an investigational drug found to lower fracture, breast cancer, stroke, heart attacks, but increased clots.

Manipulating the hormonal milieu is a tricky proposition, but future generations of "estrogen modulators" might just strike the right balance for multiple health effects.

For more on HRT and the risk of breast cancer, read "The HRT Connection" from Fall 2007.

• Two new drugs approved, one pulled from the pipeline
• Cancer screening rates low
• A call for more pancreatic cancer research
• An introduction to cancer: From a father and his daughter
• The cushion of silence

Health care reform -- Is there a Top 10 list?

BY DEBU TRIPATHY | MARCH 5, 2010

With all the political debate and drama regarding health care reform, the forgotten party, of course, is the general public - the consumer of health care. With a massive bill still in play, there appears to be an "all or nothing" mentality. Perhaps the public really deserves incremental improvements, starting with areas of consensus rather than seismic change in health care that carries a staggering price tag.

What, then, would be at the top of our list? I can give this a try:

> For one, people who already have insurance should count on coverage without worrying whether a disease was called pre-existing or not (fortunately, this is included in the House version of the bill).

> Second, if there is a public or minimal cost option, we should take advantage of a fresh start and offer coverage for a defined range of care that is clearly cost effective - for example, prenatal care, vaccinations, screening and treatment of hypertension and diabetes, and screening for cervical cancer. Of course, going down this path requires that comparative effectiveness research is carried out to serve as a basis for making these decisions.

> Third, waste and duplication should be addressed - starting with Medicare and other federally funded programs. This will require data systems and electronic medical records such that payment to hospitals and doctors would be contingent on electronic reporting (the government missed the boat years ago when it could have mandated this type of reporting for payment).

I could go on and on, but the point is that slow and steady progress with reform, starting with "low-hanging fruit" where there is agreement and a large impact from a small degree of change, is a much more preferable route than what we have now.

What will this mean for cancer care? Most likely it means that the emphasis will be on early detection and proper treatment for early-stage or curable cancers. Next would be strategies that improve survival and quality of life. Treatments that delay progression of cancer but do not impact survival or quality of life might not get covered - at least by lower cost insurance (or public options). Same for diagnostic tests that have not proven to improve outcome (there is a large list of these). However, as is the case with other technical fields, the avant-garde and unaffordable innovations would drift into greater availability and lower cost over time if the rules of the game were changed.

Whatever becomes of the health care bill, we must stay engaged with our lawmakers to press for the most important changes - one step at a time.

• Two new drugs approved, one pulled from the pipeline
• Cancer screening rates low
• A call for more pancreatic cancer research
• An introduction to cancer: From a father and his daughter
• The cushion of silence

San Antonio Breast Cancer Symposium: What have we learned and where are we going?

BY DEBU TRIPATHY | DECEMBER 14, 2009

Any high-impact scientific meeting will end with a sense of new direction, priorities for research, and expectations for clinically meaningful advances in the coming years. Based on presentations over the last few days, we may see new candidate risk stratification or diagnostic markers, such as blood microRNA and optical imaging. The impact of MRI screening and diagnosis will be better understood. We could see further studies looking at the preventive nature of metformin and other strategies that affect energy balance.

The number of settings in which we use gene profiling tests and the number of assays available will likely grow. Hormonal therapy regimens will probably not change since key trials assessing oophorectomy will not be out for some time, but better guidance may arise from assays such as CYP2D6 which for now gives conflicting results in relationship to the effectiveness of tamoxifen --as well as factors that may tell us who is at most risk for toxicities and noncompliance of therapy.

The impact of bisphosphonates and newer bone-targeting agents on risk of cancer, risk of recurrence, as well as on bone metastases should all be better characterized, with results from a pivotal study in the adjuvant setting which will likely influence practice for a large proportion of patients. There is now more evidence to use Herceptin with chemotherapy instead of after it, and more confirmation that non-anthracyline regimens with Herceptin are safer on the heart and probably just as effective--so it is hoped that better clinical and biomarker factors will emerge to tailor therapy in this situation.

The line of therapy and the drugs which we combine with the anti-angiogenic antibody Avastin will probably change in the eyes of some oncologists but not others. Newer anti-HER2 therapies will be further expanded into clinical trials, with the possibility of some of the more effective and less toxic drugs even being approved for compassionate use. The same holds true for drugs like poly (adenosine-diphosphate-ribose) polymerase (PARP) inhibitors. However, many other newer drugs like anti-angiogenic tyrosine kinase inhibitors face an uncertain future due to modest or negative results, and will need to further study. Fundamental discoveries about cancer progression and mechanisms of drug action and resistance are being translated into newer therapies--those expected to generate phase I or II trial data in the next year include PI3 kinase inhibitors, insulin-like growth factor receptor inhibitors along with Notch and other stem-cell pathway modulators.

Newer insights on meeting the needs of survivors and incorporating the needs of patients and advocates into research, clinical trial awareness/accrual, and public policy will continue to emerge as they have this year. This meeting will certainly continue its unique multi-disciplinary role in the breast cancer community through the inclusion and active participating of all its constituents in the presentation, interpretation, and the application of new data.

To read the rest of CURE's coverage of SABCS 2009, visit sabcs2009.curetoday.com

• More trail mix
• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• The big news from the American Society of Hematology

Updates on treatment for HER2-positive breast cancer

BY DEBU TRIPATHY | DECEMBER 13, 2009

In this morning's session, two updated results were presented on HER2-positive breast cancer.

The first one was a trial that compared the HER2 kinase inhibitor, Tykerb, alone or in combination with Herceptin in patients who had already progressed on Herceptin therapy. This strategy of "dual" blockade of the same target (HER2) is based on the notion that resistance to Herceptin might be overcome with Tykerb since it acts on a different part of the HER2 protein. This appears to be the case in the laboratory, and this study was reported earlier, showing an increase in the time to progression with both drugs compared to Tykerb alone.

This follow-up study was to look at survival, which was confounded by the fact that three-quarters of the patients who progressed on Tykerb had Herceptin added to their treatment, possibly diluting any survival difference. Still, this study showed an improvement in survival with dual blockade, about five months longer--this was statistically significant. Serious cardiac side effects were uncommon, 2 percent in the combination arm. This is the only study that has shown a survival advantage in patients who have progressed on Herceptin or with combination targeted therapy; therefore, the presenter, Dr. Kimberly Blackwell, felt that this all-biological regimen was a reasonable choice for patients in this setting, in addition to the approved Xeloda plus Tykerb regimen.

This study was followed by a presentation of the BCIRG 006 trial that examined Herceptin added to chemotherapy in the adjuvant setting. This study was unique among the four major adjuvant trials in that it tested a regimen (known as TCH, for Taxotere, carboplatin, and Herceptin) that did not include Adriamycin, a standard chemotherapy drug that can cause heart failure when used alone and can accentuate this side effect that is also caused by Herceptin.

The question that has not been fully answered is whether this regimen is equally as effective as the more standard combination of Adriamycin plus Cytoxan followed by a taxane plus Herceptin (AC/TH). The TCH regimen has already been adopted widely as it causes less heart side effects, and the final results of the update did indeed confirm that TCH was as good as AC/TH, with both these regimens being superior to the non-Herceptin comparator regimen of AC/T. While there were slightly more recurrences with TCH compared to AC/TH, this was not statistically significant. In addition, the small risk of leukemia that is known to occur with Adriamycin was not seen with TCH (except in one patient diagnosed with lymphoma after breast cancer and was treated with Adriamycin prior to developing leukemia).

According to the presenter, Dr. Dennis Slamon, who has spearheaded the scientific and clinical development of HER2-targeted therapy, TCH can now be considered as effective even for high-risk HER2-positive early stage breast cancer. The subgroup of higher risk patients with four or more nodes showed similar outcomes with either Herceptin-containing regimen. He also showed some controversial information about patients who exhibit gene amplification of topoisomerase II, a cell cycle-dependent gene that is also a target of Adriamycin, and is seen in about one third of HER2-positive cases. These patients appear to be sensitive to Adriamycin such that they do not even appear to benefit from adding Herceptin, with all three regimens being equivalent in this patient subset. He still favors TCH for this group given the absence of leukemia risk seen with the two other regimens (AC/T and AC/TH).

To read more articles from CURE's coverage of SABCS 2009, visit sabcs2009.curetoday.com

• More trail mix
• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• The big news from the American Society of Hematology

The importance of cellular pathways and updates on anti-angiogenic drugs

BY DEBU TRIPATHY | DECEMBER 11, 2009

Today's morning session started off with a heavy dose of basic science--two important pathways were discussed. One is a key driver of cell growth that originates from growth factor receptors and is transmitted through an enzyme called PI3 kinase. This pivotal enzyme is regulated (or turned off) by another enzyme called PTEN. It turns out that there are mutations in PI3 kinase as well as PTEN that can deregulate this pathway and lead to cell growth and also resistance to growth factor receptor antibody drugs. While we are years away from new therapies in the clinic, there are already PI3 kinase inhibitors in clinical trials.

Another pathway is less understood and leads to a cellular transformation termed epithelial-mesenchymal transition, whereby tumor cells may actually evolve into more difficult to treat cancer stem cells. Stem cells are thought to be responsible for recurrence and drug resistance, but newer drugs that target stem cells are now in clinical trials. Dr. Jenny Chang presented both animal and human clinical trial tissue-based data that preliminary shows effectiveness of these drugs at the cell level. Of course, the final proof of these drugs will be in later trials that will be ongoing over the next few years.

The afternoon session reviewed a follow-up of a trial of Avastin that showed an improvement in progression-free (but not overall) survival when added to the chemotherapy Taxotere for metastatic breast cancer--confirming early results. A newly presented trial, Ribbon II, examined Avastin in patients who had already received chemotherapy for advanced disease (second line) and showed that in this situation, Avastin can also delay progression when added to several types of chemotherapy (taxanes and capecitabine). This might expand the settings in which Avastin can be used, but several audience members questioned whether the lack of a survival benefit should justify the routine use of Avastin.

New anti-angiogenic kinase inhibitors are being tested in addition to chemotherapy and two trials of the drug Nexevar, already approved for kidney cancer, were tested in addition to Xeloda or Taxol in two separate studies, compared to chemotherapy alone. The Taxol study showed a very slight benefit, but the Xeloda study showed a clear improvement in progression-free survival. Both of these were smaller trials and not the type that the FDA would review for approval, but will probably lead to more definitive studies. In both cases, side effects were rather prominent, especially with hand/foot syndrome seen in the Xeloda study--although the presenting investigator, Dr. Jose Baselga, felt that these could be lessened with closer monitoring and more rapid dose adjustments. The general theme of how small of a benefit is worthwhile was again brought up--especially in light of the side effects. The larger trials will have formal quality of life analyses. Another anti-angiogenic kinase inhibitor, sunitinib, also already approved in kidney cancer was compared to Xeloda, both drugs given by themselves, and somewhat surprisingly, Xeloda was better than sunitinib. So this drug will probably not be further developed for breast cancer, at least not as a single agent.

To read more articles from CURE's coverage of SABCS 2009, visit sabcs2009.curetoday.com

• More trail mix
• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• The big news from the American Society of Hematology

Bisphosphonates and breast cancer risk

BY DEBU TRIPATHY | DECEMBER 11, 2009

Breast cancer prevention can be accomplished with tamoxifen, and this cuts the risk by about one-third to one-half, but very few women actually choose to go this route--in part, due to side effects. Dietary prevention studies have been negative as well, although with longer follow-up, we may find some benefit with very low-fat and high-vegetable diets.

But what about bisphosphonates? These drugs are already approved for osteoporosis as well as for patients with bone metastases. There is now some evidence that these drugs might prevent recurrence in patients with early stage breast cancer and definitive studies examining this will be out soon. Dr. Rowan Chlebowski presented data from a series of studies in 151,000 postmenopausal women that were studying diet, hormonal replacement, vitamin D, and calcium replacement. He looked at the small fraction of women who happened to be taking bisphosphonates for low-bone mineral density, and using the appropriate statistical adjustments, he found that the risk of breast cancer was lowered by about one-third.

This is very intriguing information about a completely new way to lower breast cancer risk, but this type of analysis cannot fully assure that other factors might account for the lowered risk. For example, these patients also weighed less than average, and while the analysis attempted to correct for many such factors, it is impossible to fully correct for unknown factors that may also be associated with bisphosphonate use. Still, this is a very compelling analysis and needs to be studied formally in a prospective trial, as a separate case-control study of patients in Northern Israel presented at the same session showed similar results.

Individuals carrying BRCA1 or BRCA2 mutations are at very high risk of breast cancer, and MRI screening appears to be more sensitive in picking up cancers compared to mammogram in this population. During an SABCS session on Thursday, Dr. Ellen Warner reported on a large group of such patients who underwent regular MRI screening at Sunnybrook Regional Cancer Center in Toronto who were compared to a group of similar patients at several centers who only had mammographic screening. The purpose of this study was to verify that patients screened by MRI and mammography would be picked up at lower stages of cancer compared to mammography alone.

This study did indeed show that the average tumor size with MRI screening was 9 compared to 18 millimeters and that more patients had in situ (pre-invasive) or stage 1 cancers with MRI screening, whereas those who had mammographic-only screening had more stage 2 and 3 cancers. While this study does not definitely prove that MRI screening will lead to better curability of cancer in the setting of BRCA mutations, it does provide more support for this approach--one that is already recommended by the American Cancer Society as well as other organizations.

To read more articles from CURE's coverage of SABCS 2009, visit sabcs2009.curetoday.com

• More trail mix
• When the cancer comes back
• Two new drugs approved, one pulled from the pipeline
• Emerging treatment option for myeloma presented at hematology meeting
• The big news from the American Society of Hematology