Is advanced breast cancer really increasing in younger women?


Debu Tripathy blog image
A high-profile article was published recently showing a small but statistically significant increase in the rate younger women, aged 25-39 diagnosed with breast cancer with distant metastasis. Published in the Journal of the American Medical Association (JAMA), it's made quite an impact (you can read the full article here). But what are we to make of this, and should anything be done? Should we be alarmed? Well, probably not at this point – it may not even be real.

First of all, this information comes from cancer registry data, which is very good at capturing data at the time of diagnosis, but not long-term follow-up (other than death). So this is really looking at the less common situation of women who actually present with metastases at the time of their original diagnosis – which only happens about 5 to 10 percent of the time, and perhaps more so in women who do not have access to health care and present with higher stage cancers.

Second, the overall numbers are very small – going from 1.53 to 2.21 cases per 100,000 women per year from 1976 to 2009. In the same period of time, there was an also an increase, although small, in this measure for women age 40-54, but not for those age 55 to 84.

Finally, there has not been what would be an expected corresponding disproportional increase in death due to breast cancer reported among younger women over this timeframe, so other causes, such as more aggressive use of CT and PET scans in younger women could account for this - such that the true incidence is not changing, we are just being made aware of it more due to scanning.

Of course, these data do not tell us WHY we might be seeing this increase, or whether we can even verify it. So for the moment we need to look at other information sources and worldwide statistics. We also have to determine if there might be addressable causes, such as limitations of access to care in this population, known as AYA (adolescent and young adult). AYAs do have more barriers to care and other studies have shown that they have not benefited as much with improvements over time in cancer mortality compared with pediatric and older adult populations. More AYAs have no or limited insurance. They are also more mobile and their medical follow-up may be inferior.

While this report should not cause alarm or even affect any of our care guidelines, it may be a wake-up call to truly understand what might be driving this.


Personalized medicine and what it means


Personalized cancer medicine has become a major buzzword as of late, but what does it really mean?

Everyone defines it differently, so the bird's eye view of this term would be as encompassing as possible. On one level, it means that every patient is an individual and that their course through the diagnosis and treatment of cancer should reflect their values and preferences within the boundaries of medical evidence that is works. The way information is communicated, the way different choices are presented, and even how treatment choices are balanced against side effects (sometimes permanent), all need to be customized.

A mother of two young children and a professional violinist might make very different treatment decisions about using a chemotherapy agent that causes neuropathy even if the benefit (improvement in cure rate) is identical. Similarly, the medical care team needs to formulate tailored strategies to keep patients satisfied with treatment, compliant with medications and educated about when to call with side effects. Using a one-size-fits-all approach will probably lead to much lower performance in all these departments.

A very different definition of personalized medicine is the high tech world of genomics and proteomics that exposes unique vulnerabilities in an individual's cancer. Just in the last year, massive amounts of genomic information from the tumors of many patients has been made available through publications and databases-–analyzing this fire hose of data is starting to reveal that cancers do in fact harbor many genetic "drivers," and the next step will be to squelch these with targeted drugs. Also, deciphering inherited variations the drug metabolizing enzymes will help us predict who is more susceptible to drug side effects--further customizing treatments.

The best model of personalized medicine is one that integrates all these definitions to create an environment that revolves around the patient. This includes a rationally composed and individualized treatment plan using the best science along with supportive approaches that add up to a holistic plan that is reflective of the individual. Let's hope that health care reform will encourage and incentivize personalized medicine for cancer.


Small gains in pancreatic and gastric cancers add up


Two small steps forward emanated from the ASCO Gastrointestinal Cancers Symposium going on this week, and they both raise the difficult issue of very small gains and what they mean.

In patients with advanced pancreatic cancer, the addition of the chemotherapy agent Abraxane (albumin-bound paclitaxel) to the standard chemotherapy Gemzar (gemcitabine) improved survival by a median of a little under two months. There are no standard therapies for stomach cancer in the second line, and in another study presented, the use of Taxotere (docetaxel) in this setting improved survival by a median of 1.5 months.

What are we to make of these small gains? Are they worthwhile? The answer depends on who you ask, but from my perspective as a medical oncologist, these are truly welcome advances. First of all, we have to recognize that these are average gains, and for a small number of patients the gains could be much longer--maybe exceeding a year. Second, while we recognize that side effects and financial costs have to be reflective of the overall benefit, we also know that these small steps add up, and more importantly lay the foundation for bigger improvements down the line.

We never would have enjoyed the success of drugs like Herceptin for breast cancer or stem cell transplant for leukemia if it were not for the chemotherapy underpinnings that themselves may not be as glamorous or ground-breaking, but are very important components of treatment. However, as we help our patients and families through difficult treatment decisions, we have to be very frank about the projected risks and benefits and must have realistic expectations to temper the hope we all naturally experience.


One year of Herceptin optimal for HER2-positive breast cancer


On one of the final days of SABCS there was some interesting updates to Herceptin.

Seven years ago, the original data on Herceptin in early-stage breast cancer was presented. This year, there was an interesting update to the U.S. trial that was presented. That confirmed that Herceptin is saving lives. We now have fewer deaths and fewer recurrences because of this drug. With longer follow-up, the certainty we have with the data is even greater.

Two studies looked at the duration of Herceptin. One study looked at giving Herceptin for two years and another study looked at giving it for less time, for six months. That trial found that results were worse, especially for patients given Herceptin after chemotherapy, which we usually don't do in the U.S. Here in the states, the drugs usually overlap. In that setting, when Herceptin is given for six months, the results were borderline statistically inferior, meaning one year still appears to be a little better than six months. But that's still important because 10 to 15 percent may have to discontinue Herceptin early because of side effects. These results make that decision a little easier knowing that six months of Herceptin still provides some benefit.


How do we treat local recurrence of breast cancer?


On the third day of SABCS, one study gave us another answer on how to treat local recurrence of breast cancer. We also learn more about the role of radiation in breast cancer treatment.

View the video below to get more insight into these breast cancer studies presented at the San Antonio Breast Cancer Symposium.


Study confirms higher dose of Faslodex needed


In the area of hormonal therapy yesterday, there was a trial for metastatic breast cancer patients who were receiving Faslodex. This drug has been shown to delay progression and is now a standard of care. Unfortunately, we haven't really nailed down the optimal dose yet.

When it was first approved, it was approved at 250 mg due to the early trials of the drug, but it quickly became apparent shortly thereafter that 500 mg seems to give you the levels you might want to inhibit breast cancer growth.

Several years ago, a trial was launched comparing the two dosages. That trial, which was presented a couple of years ago, did establish 500 mg as the proper dose. At this year's SABCS, updated results showed that the higher dose improves survival. There is an improvement in the mortality rate even after patients progress and go on to other drugs.

Most oncologists are using the higher dose now, but this study provides us a greater justification to use 500 mg. Fittingly, the trial is called CONFIRM.


Should women take 10 years of tamoxifen to prevent breast cancer recurrence?


At this year's San Antonio Breast Cancer Symposium, a long-term study of tamoxifen was announced. This study, called ATLAS, looked at women who took more than five years of tamoxifen after breast cancer. There has been a lot of interest in whether more than five years of tamoxifen is beneficial in reducing the risk of recurrence or breast cancer death and this study helped answer that question.

It showed that there is a 3 percent drop in mortality rate and about a 3-4 percent drop in recurrence rate. And it didn't become apparent until 10 years after randomization. It's a delayed effect.

But this is good news. It means we do have another tool for longer-term therapy that can further lower the risk of recurrence, but it mostly pertains to women who are still premenopausal (otherwise we would use a new class of drugs called aromatase inhibitors).

So, now when women hit the five-year mark of tamoxifen, they should check with their doctors to see if more hormonal therapy might be indicated in their case.

Watch Dr. Tripathy's full opinion about the ATLAS study below.


Do you understand the goal of your cancer treatment?


The New England Journal of Medicine tends to publish larger and higher impact studies that will affect standards of care, but they also will print eye-opening studies that tell us something unexpected and give us pause for thought.

A very important survey appeared in the Journal recently – it was part of a larger study that explored the attitudes and knowledge of patients with colorectal and lung cancer. This analysis of patients with advanced metastatic cancer who opted for chemotherapy showed that most patients had unrealistic expectations of cure – something that is rare in metastatic cancer. This is in contrast to earlier studies, many of which were done at larger and specialized cancer centers, which showed that most patients understood that cure was not likely.

What does this study say about patients being seen in clinical practice that reflects the average across the United States? At initial glance, it appears that patients are not adequately informed or do not fully understand their accurate prognosis. However, it is difficult to interpret results of questions asked or over the phone and to surrogates who answer in the patient's stead as was the case in this study. This study was not designed to delve into the complexities of patients' levels of hopes and understanding about their disease. Still, there are important lessons for us all in these results.

A higher expectation of cure was seen in patients who were non-white, or had colorectal cancer, and interestingly, who reported better communication with their physician. It means that physicians need to use better educational methods, but still retain their patients' trust and confidence. We live in a time where technology keeps pushing the envelope on outcomes in cancer, but where cure of many common cancers in the metastatic setting is still fleeting. The public needs to make fully informed decisions about their health care – whether it is for metastatic cancer or open heart surgery for coronary artery disease.

In this age of information at one's fingertip, this should be much more achievable, but on the other hand, the savviest of readers needs a guide in the informational jungle. CURE's special edition on metastatic cancer, which will be available in December, aims to educate with compassion, realism and hope – we believe that all of these are mutually compatible.


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