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CATEGORIES [ FEATURED ]

Sorting out the low-risk cancers

BY DEBU TRIPATHY | AUGUST 19, 2014

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There is so much attention on the aggressiveness and dangers of cancer – and rightly so, as it is a major cause of death in our society. However, there is a flip side to this story – a diverse group of low-risk cancers, or "precancers" that could in some cases even be better left undiagnosed, as the treatment may actually cause more harm than good. These types of malignancies include diagnoses like "in situ" or "non-invasive" cancers that are commonly seen in the breast, prostate and cervix, or "borderline ovarian tumors."

In many cases, they do not have the potential to invade other tissue or to spread, so they don't carry the same risks of illness and death. Some have even advocated that we rename these diseases without using the words "carcinoma" or "cancer," which bring out fear and anxiety and also motivate patients, as well as clinicians, to carry out more aggressive treatments.

However, these low-risk cancers can sometimes co-exist with more dangerous invasive (or infiltrating) cancers, and as they are typically treated with surgical removal, there can still be recurrences over the course of time, which can be either in situ or invasive. They rarely can result in death. However, these bad outcomes are unusual enough that when one looks at large population statistics for many of the in situ types of cancer, survival rates are indistinguishable from the normal population.

So, what are medical experts and even some patient advocates now saying?

The messages are mixed as there is controversy that balances the small risks of these cancers against side effects of diagnosis and treatment. For one, there are calls for modifying our cancer screening procedures – this is particularly true for breast and prostate cancer, where "overtreatment" of harmless cancers carry significant short- and long-term side effects. We also need to develop better imaging and tissue-based tests to identify the rare aggressive cancer hiding among a sea of low-risk cases. Finally, we need to make sure that physicians and the public are up to date on the latest recommendations and developments in this area, as it will continue to evolve.

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CATEGORIES [ ASCO, BREAST CANCER ]

ASCO: Early studies show promise in treating metastatic breast cancer

BY DEBU TRIPATHY | JUNE 4, 2014

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Debu Tripathy, CURE's editor-in-chief, is in Chicago for the annual meeting of the American Society of Clinical Oncology and is reporting on the latest in metastatic breast cancer. There are several targeted drugs that are being tested in early studies that appear promising.

"A new drug, known as AMG-386 or trametinib, is being tested with taxol. At early glance seems to be a very active combination," he says. "But this is really an incomplete observation. We'll need to see how long these remissions last and how they compare to other drugs."

The class of drugs called CDK4/6 inhibitors are also being looked at closely by scientists. "In hormone receptor-positive cancers, these drugs have already shown pretty big improvements in disease-free outcomes and may be on the verge of approval," he says. One drug is also being tested in triple-negative breast cancer.

The usefulness of PARP inhibitors is still being explored for patients with metastatic breast cancer in women with BRCA mutations. A recent study of veliparib is now reporting results that show it may have activity in patients with BRCA 1 or 2 mutation.

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CATEGORIES [ ASCO, BREAST CANCER ]

ASCO: More answers, and questions, on best hormonal therapy for early-stage breast cancer

BY DEBU TRIPATHY | JUNE 4, 2014

Debu Tripathy blog image

Debu Tripathy, CURE's editor-in-chief, is in Chicago for the annual meeting of the American Society of Clinical Oncology.

He explains an analysis of two early-stage breast cancer studies in premenopausal women. The study revealed that exemestane was better than tamoxifen in patients who had ovarian blockade. After four years there was a reduction in recurrence risk, as well as a slight increase in survival. An analysis that would compare these results to tamoxifen alone is still awaited.

"We're not quite ready to change hormonal therapy for all premenopausal women," he says. "But that may end up being the case; we may know more in about six months."

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CATEGORIES [ ASCO, BREAST CANCER ]

ASCO: Study shows Herceptin still best bet in HER2-positive, early-stage breast cancer

BY DEBU TRIPATHY | JUNE 4, 2014

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Debu Tripathy, CURE's editor-in-chief, is in Chicago for the annual meeting of the American Society of Clinical Oncology. He explains the clinical implications of the ALTTO study, which examined Herceptin (trastuzumab), Tykerb (lapatinib), Herceptin and Tykerb, or Herceptin followed by Tykerb.

"It essentially showed no statistical difference in the overall disease-free survival rate," he says.

"It was a little bit of a disappointment because we obviously want to improve on the benefit of Herceptin alone. And, also, we had early indications that maybe we would see a benefit. There were a series of neoadjuvant trials (so-called pre-operative trials where the chemotherapy is given before surgery) where we compared the number of patients who had a complete disappearance of their tumor. Earlier studies, that were of the same design, had shown that when you combine Herceptin and lapatinib that you nearly doubled the number of patients who had a complete response. We were fairly hopeful that this would translate into a real clinical benefit."

While the analysis is not complete, and we still want to examine whether a subgroup of patients benefits, the conclusion now is that Tykerb does not add any benefit to standard Herceptin for early-stage, HER2-positive breast cancer.

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CATEGORIES [ ASCO, BREAST CANCER ]

ASCO: Bone-strengthening drugs could be given less frequently in metastatic breast cancer

BY DEBU TRIPATHY | JUNE 4, 2014

Debu Tripathy blog image

Debu Tripathy, CURE's editor-in-chief, is in Chicago for the annual meeting of the American Society of Clinical Oncology.

A study announced at ASCO found that bone-strengthening drugs given for bone metastases in advanced breast cancer could be given less frequently. Patients who had received monthly Zometa for about a year were randomized to be given intravenous Zometa every three months or the standard monthly dose. Researchers found both groups of women had the same effect. Patients on the less frequent regimen also had slightly fewer complications.

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CATEGORIES [ ASCO ]

Why ASCO matters

BY DEBU TRIPATHY | JUNE 2, 2014

Debu Tripathy blog image

Debu Tripathy, CURE's editor-in-chief, is in Chicago for the annual meeting of the American Society of Clinical Oncology. He explains why the meeting is so important to clinicians and patients, as well as to the broader oncology community.

"This is one of the most important hallmark meetings of our profession. It is where the latest updates are presented and also debated," he says. "Ultimately, it's the clinicians and the sometimes the patients who have to decide on what's incorporated into standard care."

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CATEGORIES [ FEATURED, BREAST CANCER ]

AACR update: Breast cancer studies offer more potential treatment options

BY DEBU TRIPATHY | APRIL 10, 2014

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Two studies announced at this year's annual meeting of the American Association for Clinical Research are targeting unique molecular features that drive breast cancer. One study is testing the drug palbociclib, which targets an abnormality in the cancer cell cycle. The drug is being tested in hormone-positive breast cancer in combination with the aromatase inhibitor, Femara (letrozone). The combination significantly delays the time it takes for the cancer to continue growing. At the current time, it's not showing a survival advantage, but a phase 3 trial in progress may be the deciding factor for the drug's approval.

Another study is looking at a drug called neratinib, specifically in HER2-positive breast cancers. It's part of the I-SPY2 study, which is testing multiple new therapies before surgery, as neoadjuvant therapy. The results show that neratinib can result in complete disappearance of the tumor. This may represent a new drug for patients with HER2-positive breast cancer, including patients who have progressed on other HER2-targeted therapies.

Debu Tripathy is an oncologist and editor-in-chief of CURE. He is the co-leader of the Women's Cancer Program at Norris Comprehensive Cancer Center and Professor of Medicine at the Keck School of Medicine at the University of Southern California.

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CATEGORIES [ LUNG CANCER ]

AACR update: New immunotherapy drug shows benefit in lung cancer

BY DEBU TRIPATHY | APRIL 9, 2014

Debu Tripathy blog image

One of the areas that has progressed quite a bit recently is that of tumor immunotherapy. At this year's annual meeting of the American Association for Clinical Research, several papers have been presented in this area.

One of the most exciting is advances in lung cancer, which has been a traditionally hard to treat cancer. Recently there have been newer targeted therapies that work against growth factor receptors that show benefit, particularly in non-smokers. And now we're seeing advances in immunotherapy.

Now, a fundamental breakthrough in immunology has come with understanding the controls of the immune cells that allows us augment the natural immune response that white cells have against tumors.

One of the proteins blocked is the PD-1 receptor and PD-1 ligand. These proteins are important because the cancer cells can use them to block the immune system from attacking the cancer. There are several drugs being tested that inhibit this blockade, the so-called immune checkpoint, in trials not only for lung cancer, but also melanoma and other solid tumors.

One of the potential benefits of one of these drugs called MK-3475 is that it may work in people who have a history of smoking, people who have traditionally not benefited from these targeted therapies.

There is also some new information that we may be able to identify patients who have the best chance of responding to these drugs. There will be a more formal comparison and information on how the drug works in smokers coming hopefully very soon. We expect to hear those results at the annual ASCO meeting this summer.

Debu Tripathy is an oncologist and editor-in-chief of CURE. He is the co-leader of the Women's Cancer Program at Norris Comprehensive Cancer Center and Professor of Medicine at the Keck School of Medicine at the University of Southern California.

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CATEGORIES [ BREAST CANCER ]

Bisphosphonates to prevent breast cancer recurrence

BY DEBU TRIPATHY | FEBRUARY 14, 2014

Debu Tripathy blog image

Sometimes advances in treatment come suddenly with the results of one major trial, but in the case of bisphosphonates--drugs used to treat bone thinning or bone metastases--the information has been trickling in slowly.

For over a decade, studies in early-stage breast cancer have hinted that the risk of metastatic recurrence can be lowered with bisphosphonates. We still don't know exactly how a bone-targeting drug could prevent recurrence. One clue comes from that fact that these drugs seem to lower the number of microscopic cancer cells that are sometimes seen in the bone marrow of patients--even those that may never actually develop metastases. However, patients who harbor these so called "micrometastases" do have a higher risk of developing breast cancer. It has been postulated that the bone may serves as the "soil" to support the "seed," in this case tumor cells, that can then go on to form metastases. It is therefore thought that bisphosphonates, which are known to lower the resorption and turnover of bone minerals, may therefore make the "soil" less hospitable to tumor cells.

However, large randomized clinical trials of bisphosphonate therapy using the more potent newer generation amino-bisphosphonates such as Zometa (zoledronic acid) have yielded mixed results--some showing fewer recurrences and others showing no effect at all.

Finally, a clearer picture appears to be emerging from analyzing all these trials together, as was recently done in what is called an overview (or meta-) analysis. A pooling of the results of trials that involved nearly 23,000 patients demonstrates that the main impact is in post-menopausal women, or those that have their ovaries suppressed with medical therapy. In these patients, the death rate is lowered by about 3 percent over 10 years. While this difference may seem modest, it is in the same range of what some chemotherapy treatments provide for early-stage breast cancer. It is unlikely that more trials of this nature will be done, although we still await results and updates from some of these studies. The big question will be whether the medical community (and insurance companies) will heed the results of this meta-analysis when many of the individual trials were negative. This remains to be seen as revised guidelines in this area are currently being formulated by the American Society of Clinical Oncology.

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CATEGORIES [ SABCS, BREAST CANCER ]

SABCS: Advances in hormone therapies for ER-positive breast cancer

BY DEBU TRIPATHY | DECEMBER 13, 2013

Debu Tripathy blog image
One of the themes covered during Thursday's San Antonio Breast Cancer Symposium was hormonal therapies, a very important aspect of breast cancer care.

The first study I want to discuss is actually a prevention study looking at aromatase inhibitors. This class of drugs has been around for about two decades, but as a treatment for advanced breast cancer first and early-stage breast cancer a little later.

The whole idea began when researchers examined women who were taking aromatase inhibitors (AI) for early-stage breast cancer. They noticed that women on AIs had fewer cancers develop in the opposite breast, which gave them the idea that AIs could be used as a therapy to actually prevent breast cancer.

The study presented on Thursday studied women who were at high-risk for breast cancer who were given either anastrozole, which is an AI, or placebo for five years. Researchers discovered that the AI cut the risk of breast cancer by about half.

There are side effects with AIs, such as muscle pain, but in the prevention setting, the side effects didn't seem as severe as when women were taking them to treat existing breast cancer.

For now, we haven't seen any overall survival benefit, though. It could be that these drugs lower the risk of breast cancer, but whether that actually equates into saving lives is still up in the air. AIs are not currently approved for breast cancer prevention, but other breast cancer therapies--tamoxifen and Evista--are.

Another presentation went into the biology of how hormonal therapies work against breast cancer, including drug resistance in advanced disease. Hormonal therapies generally have fewer side effects than traditional chemotherapy. So, if we can delay drug resistance, women can take hormonal therapies for years with few side effects. Once the cancer does begin to spread, that's when we move to chemotherapy. But the longer women can stay on hormone therapies, the better, which is why we're trying to figure out drug resistance.

Mutations can make the estrogen receptor stuck in the on position, which can make the cancer unresponsive, or resistant, to certain hormone therapies. These mutations may have been in the original cancer, but once the hormone therapies kill the sensitive cancer cells, it may leave these few resistant cells an opportunity to begin to rapidly grow and spread. This is really the first step in trying to understand how we can counteract these mutation-carrying estrogen receptors.

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