Meditations of an oncology geek

Archive for October, 2011

Could cancer screening be harmful?

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30 October 2011

Dollar-wise, how much is a life worth? How much are we as a society willing to pay to “save” a life? Even so, are we more willing to save a life of a child than a senior citizen? A vegetable than a genius? These are examples of open-ended questions that might not ever have perfect answers, but through discussion and rational debate it might be possible to arrive at better answers.

Cancer epidemiologists have postulated for 70 years that cancer caught early could be curable by surgery (Mukherjee 2010). “Early” being defined as before the primary tumor had begun to metastasize and spread to distant organs. But even that view is not without nuances, as it is becoming more apparent that some cancers will begin to metastasize early, and some will never metastasize at all. This week Gina Kolata of the New York Times penned a curious article on how some cancer screening can be harmful.

In short, it is becoming clearer that, in the case of breast and prostate cancer, those readily caught early are also the ones that are usually slow-growing and not life-threatening. As a result, cancer screening might actually result in more surgical and chemotherapeutic interventions than necessary. Or, our current screening techniques might be unable to catch the dangerous cases of cancer.

However, no medical knowledge is inherently harmful. It is the subsequent actions (and perhaps non-actions) that can cause harm to patients. It may be that our knowledge of which cancers will begin to spread quickly and those that do not isn’t up to par. Even within breast cancer there are several distinct subclasses of the disease defined by particular molecular signatures that trigger different disease progression.

Thus, not all “breast cancer” is the same disease. Some types might metastasize and spread earlier in disease progression. Some might remain benign and not life-threatening. Better characterization of such will allow not only for early detection, but better plans of action for treatment, or non-treatment.

-Ryon

Written by Ryon

October 30th, 2011 at 4:31 pm

Posted in Science Blog

Fighting fire with gasoline? Did alternate cancer therapies shorten the life of Steve Jobs?

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23 October 2011

Jobs was a savvy businessman and one of the visionaries of our time. In his famous 2005 commencement address to Stanford University he stressed the importance of taking risks. A trickle has turned into a stream of information that suggests that Jobs may have taken an extraordinary gamble with his own life.

I admit that without Jobs’s full medical history that some of the details herein are speculation and not as scientifically rigorous as I prefer. Also, individual case studies do not meet the standards of rigorous and accurate epidemiology. However, I would like to use the available information as a cautionary tale.

Jobs was very private about his illness, and out of nearly a dozen articles, this one by Sharon Begley of NewsWeek is the most balanced and comprehensive one I could find. Jobs initially decided to forego conventional surgical treatments and using alternate (untested) therapy before undergoing conventional therapies (like surgery) once his cancer spread.

He later took another gamble: a liver transplant. One of the most common (and deadly) sites of pancreatic cancer metastasis is spread to the liver. It’s widely speculated that he swapped a cancer-riddled liver with a fresh one. Now, that’s speculation, but what isn’t speculative is that an organ transplant requires one to take powerful immunosuppressant drugs for the rest of their life. Such a move would theoretically compromise the immune system’s ability to fight the cancer.

A liver transplant in the face of cancer metastasis is like trying to fight fire with gasoline. Once cancer has begun to spread beyond the organ of origin (the pancreas for Jobs) it is likely that tumor cells have been seeded many other places beyond the pancreas and liver. It would only be a matter of time until tumors would become detectable and begin to damage other vital organs. The effect of suppressing the immune system would likely enhance the progression of the seeded tumor cells in other parts of the body by removing a roadblock for tumor growth.

Immune suppression is VERY dangerous for cancer patients. I should also note that radiation and chemotherapy can also weaken the immune system, and this caveat is a major factor in determining the proper dose and application of conventional therapies. Despite these caveats, radiation and chemotherapy have saved many lives and prolonged the lives of many more cancer patients. And, they continue to do so consistently in clinical trials.

Now, don’t get me wrong. The goal of this article is not to take a jab at Steve Jobs. The man did many, many things right in his life. The opportunity presents itself to use his medical history as a lesson for the dangers of relying on treatments that are “alternative” or “complimentary.” I have a problem with those ambiguous labels, as they are often contextually used to try to legitimize medicine that has not been proven to work consistently. If clinical trials demonstrate efficacy, therapies cease to be labeled “alternative” but are instead: medicine.

-Ryon

Written by Ryon

October 23rd, 2011 at 8:19 am

Posted in Science Blog

Can pregnancy prevent breast cancer?

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16 October 2011

Commentary on original research

In the spirit of breast cancer awareness month, I thought I’d make my readers more aware of a phenomenon that has a very pronounced influence on a woman’s lifetime breast cancer risk. This phenomenon could account for up to a third of breast cancer risk factors. To put that in perspective, genes and genetically inherited breast cancer risk accounts for at most 10% of all breast cancer risk in a population. This phenomenon I am about to discuss is currently, in my opinion, the most plausible mechanism for the increased rates of breast cancer in first world countries as well.

Here it is: pregnancy. (1)

Younger age of first tull-term pregnancy and number of pregnancies are strongly associated with a reduction in lifetime risk of breast cancer.

The article’s abstract is included below:
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INTRODUCTION:Although pregnancy-related factors such as nulliparity and late age at first full-term pregnancy are well-established risk factors for invasive breast cancer, the roles of these factors in the natural history of breast cancer development remain unclear.
METHODS:
Among 52,464 postmenopausal women participating in the California Teachers Study (CTS), 624 were diagnosed with breast carcinoma in situ (CIS) and 2,828 with invasive breast cancer between 1995 and 2007. Multivariable Cox proportional hazards regression methods were used to estimate relative risks associated with parity, age at first full-term pregnancy, breastfeeding, nausea or vomiting during pregnancy, and preeclampsia.
RESULTS:
Compared with never-pregnant women, an increasing number of full-term pregnancies was associated with greater risk reduction for both breast CIS and invasive breast cancer (both P trend < 0.01). Women having four or more full-term pregnancies had a 31% lower breast CIS risk (RR = 0.69, 95% CI = 0.51 to 0.93) and 18% lower invasive breast cancer risk (RR = 0.82, 95% CI = 0.72 to 0.94). Parous women whose first full-term pregnancy occurred at age 35 years or later had a 118% greater risk for breast CIS (RR = 2.18, 95% CI = 1.36 to 3.49) and 27% greater risk for invasive breast cancer (RR = 1.27, 95% CI = 0.99 to 1.65) than those whose first full-term pregnancy occurred before age 21 years. Furthermore, parity was negatively associated with the risk of estrogen receptor-positive (ER+) or ER+/progesterone receptor-positive (PR+) while age at first full-term pregnancy was positively associated with the risk of ER+ or ER+/PR+ invasive breast cancer. Neither of these factors was statistically significantly associated with the risk of ER-negative (ER-) or ER-/PR- invasive breast cancer, tests for heterogeneity between subtypes did not reach statistical significance. No clear associations were detected for other pregnancy-related factors.
CONCLUSIONS:
These results provide some epidemiologic evidence that parity and age at first full-term pregnancy are involved in the development of breast cancer among postmenopausal women. The role of these factors in risk of in situ versus invasive, and hormone receptor-positive versus -negative breast cancer merits further exploration.

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This article came out in December of last year. I had heard of this phenomenon before, but I had not seen a study done so tightly until I found this one. Over 52,000 women in California took part in the study, and it found a few associations:

1) The earlier a woman has her first full-term pregnancy, the lower her lifetime breast cancer risk
2) The more pregnancies, the lower her lifetime breast cancer risk.
3) There is an exception to #2: women who have their first child at age 35 and over had the opposite effect: compared to women who had their first child before age 21, they had a 118% increased chance of developing dicta carcinoma in situ, and a 27% increased chance of developing invasive (and likely deadly) breast carcinoma.

This study is one of large-scale association. In many ways, it has stronger statistics than many of the odd cancer theories circulating on the web. This study was done by reputable scientists at a reputable cancer research institute (City of Hope) funded by reputable sources and published in a peer-reviewed journal. It does not, however, contain experiments to determine a mechanism. Those studies are currently underway.

Compared to women in third-world countries, women in first-world countries have less pregnancies and often delay childbirth until later in life. Women in first world countries also develop breast cancer more frequently (2). It is hard not to postulate that the two are related. Keep in mind that these data are all about the incidence (development) of breast cancer and not the treatment of breast cancer. That is another topic.

So, what if you’re a woman who is at increased breast cancer risk, given the article I presented? You need to do this: talk to your doctor. That’s it. For your next physical or check-up just bring it up in conversation. Go to the link and print out the first page of the article if it helps you start a conversation. Your doctor might recommend cancer screening. But the most important thing is to become aware of your personal cancer risks and begin to mitigate them. Barring not ever getting cancer, early detection is the best way to beat the disease.

-Ryon

References:
1) http://www.ncbi.nlm.nih.gov/pubmed/20565829
2) American Cancer Society

Written by Ryon

October 17th, 2011 at 3:06 pm

Posted in Science Blog

Why is Pancreatic Cancer hard to treat?

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This week marks another question from Peter Borak of San Francisco, CA:

Why are some cancers fatal and other cancers easy to treat?

This question seems quite timely given the untimely death of Apple guru Steve Jobs this week from Pancreatic Cancer.

The cancers that are easily detectable tend to be the most treatable. For instance, skin cancer is frequently curable. Like most cancers, cancers of the skin take years or even decades to develop. But, pre-cancerous lesions (funny-looking moles, for instance) are easily spotted and removed.

This stands in stark contrast to, say, cancer of the pancreas. Pancreatic cancer has a mean survival time of less than 6 months from diagnosis. The first reason why is because symptoms usually do not present until late disease. Severe abdominal pain and unexplained weakness are often conflated with other more common illnesses, like indigestion and the flu.

However, Jobs actually caught his cancer fairly early (1). He had a history of gastrointestinal problems and received scans as part of his regular physical examinations. These are expensive and uncommon to have as part of routine physicals, as it is very difficult to scan the area surrounding the pancreas.

This brings me to the second reason why some cancers are harder to treat than others: propensity to metastasize and spread. Pancreatic cancers often spread very quickly and colonize other vital organs nearby, like the liver. Once cancers begin to spread, it’s very, VERY hard to eradicate. I like to use the analogy of a weed’s spores seeding a garden. Once the weeds start to spread, it’s an uphill battle. The weeds will grow and out-compete everything else in the garden without extreme care and effort, and will consistently spring back. A tumor can shed millions of tumor cells into blood circulation per day, and any of those have the potential to wreak havoc on vital organs. Tumor cells also have the ability to remain dormant for years in distant soils of other organs, evading chemotherapy. When cancer is in this state, known as “micrometastasis” it has seeded vital organs and lying dormant, undetectable by modern medal scanning.

The third main reason why some cancers are harder to treat then others is somewhat related to the first point: surgical removal can be very difficult. I will again refer to pancreatic cancer. The pancreas is an organ surrounded by many other vital organs, making surgical removal of tumors an extremely delicate procedure. Jobs underwent the whipple procedure (2) which

“consists of the en bloc removal of the distal segment (antrum) of the stomach; the first and second portions of the duodenum; the head of the pancreas; the common bile duct; and the gallbladder.
The basic concept behind the pancreaticoduodenectomy is that the head of the pancreas and the duodenum share the same arterial blood supply (the gastroduodenal artery). These arteries run through the head of the pancreas, so that both organs must be removed if the single blood supply is severed. If only the head of the pancreas were removed it would compromise blood flow to the duodenum, resulting in tissue necrosis.”

From a logistics standpoint, it might be easier to build a ship in a bottle – blindfolded – than to successfully remove tumors from the pancreas.

Jobs had been notoriously secretive about his illness, but it became known that in 2009 Jobs had a liver transplant. The cancer research community collectively raised an eyebrow. The liver is one of the first places that pancreatic cancer metastasizes to. Given Jobs’s previous declaration that he was cured of his disease, we watched with a somber eye.

So, in general, the easier the cancer is to detect early, the greater the survival. The more difficult to detect cancers, as well as those more difficult for surgical intervention, are the ones that have higher fatality rates. As for Jobs, there is some controversy regarding the direction he took in battling his cancer, including the use of alternate therapies, like the Gonzalez procedure (3) that had been previously proven to be ineffective and even dangerous by peer-reviewed scientific studies. However, that is a discussion for another time.

-Ryon

References:
1) http://money.cnn.com/2008/03/02/news/companies/elkind_jobs.fortune/index.htm?postversion=2008030510
2) http://en.wikipedia.org/wiki/Pancreaticoduodenectomy
3) http://en.wikipedia.org/wiki/Nicholas_Gonzalez_(physician)

Written by Ryon

October 9th, 2011 at 12:37 pm

Posted in Science Blog

Dangers of Nostalgia

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A really good read on the attitude of Steve Jobs, whom I consider one of the visionaries of our time: NY Times

Nostalgia is all good and great, but it can create an unhealthy obsession with an idealized past, making it difficult to imagine a better future. It’s hard to look forward while looking backward.

Happy Friday, everyone. May your best days be yet to come.

Written by Ryon

October 7th, 2011 at 6:18 pm

Posted in Science Blog

Can Aspirin Prevent Cancer?

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1 October 2011

Ed: I realize that this is a partial re-post, but in the time since I originally posted this article my readership has grown by a large amount. Moving from the experimental to theoretical, many postulate that this mechanism of cancer suppression might explain why athletes often develop the common cancers (minus skin cancer) less frequently. But I digress…

It’s easy to think of cancer as the enemy. Cancer is not the enemy. The body is the enemy: it’s an unwilling accomplice for the development of tumors. Though counterintuitive, it might actually be beneficial to treat cancer by slightly suppressing the immune system. This paradigm might actually define the future of cancer treatment and prevention.

(Emerging studies suggest that anti-inflammatory agents like aspirin might retard or prevent cancer in seniors, like a recent one in the peer-reviewed scientific journal Lancet, see below)

Tumors are not exclusively made up of cancer cells. In fact, some tumors contain only a very small percentage of cancer cells. When you take a trip inside the tissue architecture of tumors, you often find many fibroblasts, recruited blood vessels, and immune cells (like white blood cells). On the molecular level we see a trend as well. Due to the amount of infiltrating white blood cells, if you didn’t know better, you would think you were looking at a wound, or an infection.

The current trend in cancer research is to view cancer like a wound or infection that never heals. Your immune system consists of many specialized blood cells that can literally crawl right through your tissues, and through the margins between cells to inspect cells for damage or for invading bacteria. As part of a response to wound or trauma, immune cells rush to the scene and quickly colonize the tissue. This process is called inflammation, which I am sure you, dear reader, have become familiar with at some point in your life. To the immune system, a tumor cell likely looks like some sort of blunt trauma or physical wound, but as part of our evolutionary upbringing of a species over the eons, it was important to mount a VERY robust anti-bacterial and anti-viral response to any wound. Today we have the help of antibiotics… but that is a discussion for another time.

Once immune cells clear the area of “foreign” cells like bacteria or cells damaged with viruses, they secrete mitogenic factors that stimulate cell growth! AND, they secrete factors that guard against apoptosis, the cell’s natural self-destruct mechanism. Resisting apoptosis is a hallmark of cancer.

The problem is that to the immune system, a cancer cell looks almost identical to a normal cell. The two cells differ in ways so subtle that even our awesome immune systems cannot tell the difference. Not being foreign, the default action is “repair” instead of “destroy.”

In a nutshell, the body often treats tumors like wounds, and actually nourishes it and provides it with the building blocks to grow! As proof of this concept, it is now widely accepted in the cancer biology field through numerous studies in cells, animals, and humans that mild immuno-suppression actually reduces cancer risk. An example of this theory being applied successfully is the re-purposing of the drug Rapamycin. Rapamycin has been used for forty years as an immunosuppressant with people who receive organ transplants. Recently, it has been tested and found (in much smaller doses) to have very potent anti-cancer effects as well (1).

(A little nerd trivia for you: What do giant stone heads and rapamycin have in common? They can both be found on Easter Island. Rapamycin was originally isolated from soil bacteria native to the island)

Beyond Rapamycin, there have been large-scale studies on habitual users of Aspirin as a guard against stroke and heart attack. In these long-term studies scientists have also realized that seniors who consume aspirin regularly also have a reduced risk of developing cancer (2). This type of study is long-term, double blind, with a decent control group, and is considered fairly sound.

There are many more studies currently underway investigating the use of anti-inflammants as cancer suppressors. Drugs like aspirin and rapamycin are already cheap to produce, and have been around long enough that their long-term toxicities are well documented. I personally follow these with great interest, as they have the potential for immediate positive impact in the area of cancer prevention. I will explore this topic to a greater extent in a future article.

That being said, DO NOT begin ANY drug regimen without consulting your physician. If you are young and concerned about hereditary cancer affecting you before you get old, please first read up on the genetics of cancer, and if you are still concerned, please contact a genetic counselor.

Summary: The body sees tumors as wounds that never heal, and can actually help tumors grow because the immune system aids it like it would a regenerating tissue. Reducing chronic inflammation can retard or prevent cancer development, with a proof of concept demonstrated by large-scale studies of anti-inflammants in humans.

-Ryon

Back to Cancer for Dummies main page for more topics.

References:
1) Zoncu, R, Efeyan, A, Sabatini, DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011;12(1):21-35.
http://www.ncbi.nlm.nih.gov/pubmed/21157483
2) Rothwell, PM, Fowkes, FG, Belch, JF, Ogawa, H, Warlow, CP, Meade, TW. Effect of daily aspirin on long-term risk of death due to cancer: analysis of individual patient data from randomised trials. Lancet 2011;377(9759):31-41.
http://www.ncbi.nlm.nih.gov/pubmed/21144578

Written by Ryon

October 1st, 2011 at 11:12 am

Posted in Science Blog