This week, the New York Times ran an article under the headline ‘Reducing Your Risk For Breast Cancer,’ encouraging readers to lose weight, exercise more, shun alcohol and avoid hormone therapy in order to lower their risk of developing breast cancer (Rabin, NYT).
Of course it makes good sense for women to take what practical steps they can in order to lessen their risk of breast cancer. The Times article makes many valid points and gives some sound suggestions. But in general terms, the article is yet another example of the media’s tendency to over-simplify what is in fact an extremely complex disease. Ultimately it does women no service to focus so single-mindedly on the role of personal responsibility as the primary preventive strategy while omitting to mention the much larger influence of environmental risk factors such as pollution and radiation. Apart from giving a free pass to those who are silently contributing to the burden of breast and other cancers, the media’s tendency to dwell on personal responsibility while largely ignoring known environmental contributions to the disease feeds the notion that breast cancer is at least in part a consequence of poor personal choices. This may have the unfortunate effect of fostering a ‘blame the victim’ mentality.
Genetic and Environmental Triggers
North America has the highest breast cancer rate in the world. Every year in the US, about 182,000 women are newly diagnosed with breast cancer, and about 40,500 women die from the disease. Although the incidence of breast cancer has dropped slightly every year since 2003 – the year that the widespread use of hormone replacement therapy began to decline sharply – the disease remains the second leading cause of cancer death among American women.
Inherited risk plays a part, to be sure, but its influence is relatively minor: having a close relative with the disease only accounts for 5 to 7 percent of a woman’s risk. The large majority of women diagnosed with breast cancer have no immediate family history of the disease. The fact that American women are more likely than their counterparts in most other countries to develop the disease points strongly towards environmental triggers. This is borne out by the observation that women who immigrate to the US from other countries where there are lower breast cancer rates quickly assume the same risk as American-born women.
Identifying the many potential environmental contributors to cancer risk is an enormously complicated task. One group of environmental pollutants that has earned closer scrutiny for its potential role in the development of breast cancer is pesticides.
Pesticides can influence the development of breast cancer in three main ways: They can act as a “complete carcinogen” – i.e., they can cause normal tissue to undergo irreversible changes that lead to invasive malignancy. Very few pesticides are complete carcinogens. Far more common are pesticides that can act as tumor promoters, encouraging unruly growth in an existing tumor or area of abnormality. Finally, many pesticides can act as what are called “endocrine disrupters” – that is, they are capable of mimicking hormones such as estrogen that are known to drive cancer growth, or they may interfere with normal hormonal regulation of cell growth, encouraging uncontrolled cell division. Endocrine disruption is potentially the most serious contributor to breast cancer risk.
According to the Environmental Protection Agency, more than one billion pounds of pesticides are used every year in the US. Eighty percent of this total is used in agriculture, representing an enormous environmental burden. The pesticide atrazine – a known endocrine disruptor – is one of the most widely used. Although it was banned by the European Union after studies demonstrated its endocrine disrupting capacity, atrazine continues to be the second most widely used pesticide/herbicide in the US. More than 70 million pounds of atrazine are used annually in this country, the vast majority (98 percent) for agricultural purposes, as a weed killer.
Sounding the Alarm
Although the environmental movement has long harbored concerns about the endocrine disrupting ability of atrazine, the mainstream media have on the whole been very slow to pay attention to the threat posed by this extensively used compound. But a study published on May 7 in the science journal PLoS One has directly demonstrated the ability of atrazine to interfere with the hormonal signaling mechanisms in human placental cells, once again raising questions about the possible role of atrazine in the development of breast and other hormone-driven cancers (Suzawa, 2008).
The same researchers have shown in a related study that the fish population becomes feminized in water with atrazine concentrations equivalent to those found in runoff from agricultural fields (the female to male ratio is approximately doubled). Interviewed by the online journal Science Daily, the lead author of the study, Holly Ingraham, PhD, a professor of Cellular and Molecular Pharmacology at the University of California, San Francisco, urged scientists to pay more attention to atrazine’s potential dangers. “These fish are very sensitive to endocrine disrupting chemicals, so one might think of them as ’sentinels’ to potential developmental dangers in humans,” she said.
The degree of alarm within the scientific community concerning the dangers of hormone disrupting environmental pollutants is also apparent in a report released last month by the Health and Environment Alliance (HEAL), a European umbrella group of non-governmental research organizations. This report directly questions the growing tendency to label breast cancer a lifestyle and genetic disease. “We will not be able to reduce the risk of breast cancer without addressing preventable causes, particularly exposure to chemicals,” said the author of the paper, Andreas Kortenkamp, who heads the Center for Toxicology at London University’s School of Pharmacy (Kortenkamp, 2008).
The advocacy group The Breast Cancer Fund, whose mission is specifically focused on the identification and elimination of the environmental and preventable causes of breast cancer, has also done a great deal to influence public awareness concerning the dangers of endocrine disrupters and environmental pollutants. The group publishes an annual review of the evidence – State of the Evidence 2008: The Connection Between Breast Cancer and the Environment – which is available from the organization’s website (www.breastcancerfund.org).
Scientists and advocacy groups are leading the way on this important issue. It’s time for the news media to follow suit and focus more attention on the contribution of environmental risk factors to breast and other cancers.
Ralph Moss http://www.cancerdecisions.com/
June 12th, 2008
From time to time you hear about a clinical trial for a new cancer treatment that proves so stunningly effective that evaluators are obliged to end the trial prematurely so that all the participating patients can share in the new breakthrough. Typically this kind of news is portrayed as an example of progress, a welcome glimmer of hope.
However, some cynics have quietly speculated that the real purpose of stopping such trials is not to ensure that the few hundred trial participants who are receiving the current standard treatment are given access to the new drug, but to massively benefit the drug companies sponsoring the trial. When a trial is halted prematurely, researchers are deprived of the opportunity to determine whether the drug in question might eventually prove less valuable if the trial were allowed to proceed to completion. Crudely put, by stopping clinical trials early, the trial directors might be quitting while they are ahead.
Now a European study has added some substance to that cynical view. According to this report, published in Annals of Oncology, an increasing number of cancer drug clinical trials are being stopped early, on the basis of very preliminary (and possibly misleading) evidence, and this ultimately puts patients in general at risk.
Researchers at the Mario Negri Institute for Pharmacological Research in Milan, looked at all cancer trials published in the decade between 1997 and 2007 in three major medical journals. They identified 25 that were stopped early because the drugs in question appeared, initially at least, to be working well. The trials’ reviewers thereupon demanded an early trial closure so that all participating patients could get the new medicines as soon as possible. Significantly, the Milan researchers found that about 80 percent of trials that are stopped prematurely were linked to an application for a marketing license in Europe or the United States.
“That suggests that companies have a commercial interest in stopping these trials, which may not be good for patients,” said Giovanni Apolone, MD, Head of the Laboratory of Translational and Outcome Research the Mario Negri Institute. “Without enough information [i.e., the kind that can only come from a completed trial, ed.], we don’t know if patients are really benefiting from these new drugs.” Dr. Apolone is an important voice in the field of medical ethics. In addition to his position at Mario Negri, he is Vice-President of the Ethics Committee of the European Institute of Oncology and is a National Expert at the European Agency for the Evaluation of Medicinal products (EMEA) in London (UK).
Apolone also told the British newspaper The Independent: “This suggests a commercial component in stopping trials prematurely. We are aware that trials stopped early because they are showing benefit may result in the identification of promising new treatments for patients. However, findings obtained in this way require subsequent confirmation. Without such evidence, unsafe and ineffective drugs could be marketed and patients’ health could well be jeopardized.”
Some of the drugs whose trials were stopped early are among the most heavily promoted new treatments, including Herceptin (trastuzumab) for breast cancer, Avastin (bevacizumab) for colon, kidney and breast cancer, Camptosar (irinotecan) for lung and bowel cancer, Sutent (sunitinib) for kidney and gastrointestinal cancer, Nexavar (sorafenib) for kidney cancer, and TaxolCarbo (carboplatin) for ovarian and lung cancer (Laurance 2008).
Dr Apolone said it could take years for the long-term benefits or dangerous adverse effects of a drug to become evident, but the average duration of the 25 trials that were stopped early was just 30 months. Five of these trials had enrolled less than 40 per cent of the planned number of patients. This means that decisions on drug approval and availability were based on under-powered clinical trials that were halted well before information on long term safety and effectiveness could be gathered.
In the online edition of Annals of Oncology, the Milan researchers added: “If a trial is evaluating long-term efficacy of a treatment of conditions such as cancer, short-term benefits – no matter how significant statistically – may not justify early stopping. Data on disease recurrence and progression, drug resistance, metastasis, or adverse events, all factors that weigh heavily in the benefit/risk balance, could easily be missed” (Trotta 2008).
Stuart Pocock, professor of medical statistics at the London School of Hygiene and Tropical Medicine, also told The Independent that stopping trials that showed early evidence of benefit skews the overall results and exaggerates the benefits of new anticancer drugs.
“Overall, there is an underlying bias towards exaggeration [of the results]. We can pretty reliably claim there is exaggeration going on. This is not as sober an environment as it should be. It has an aura of hot-headedness about it” (Laurance 2008).
Defenders of the early trial closure system say that these decisions to pull the plug on cancer drug trials are not made by pharmaceutical companies, and not even by the researchers who head the trials. They are generally made by outside data monitoring committees, which routinely review trial information and periodically assess progress. The data monitoring committees then make recommendations to the sponsoring pharmaceutical companies. Indeed, in the Apolone study, 19 out of the 25 trials halted early were overseen by such independent data monitoring committees.
While ideally a data monitoring committee should not include any members with contractual or financial ties to the trial’s sponsor or to the contract research organization conducting the trial, it can be difficult to find experts in the field who have no such ties. Furthermore, there is nothing to say that such outside experts are not ideologically biased in favor of quickly approving new anticancer drugs. A lot of oncologists feel that the more new drugs that are available in their armamentarium, by definition the better off they and their patients will be.
The system is thus designed in such a way that evaluators generally rush to judgment to approve new agents.
Ralph Moss, 20/04/2008. CancerDecisions.com
April 20th, 2008
“Hormone replacement therapy (HRT) has been implicated as a risk factor for breast cancer and the use of HRT has decreased substantially in general population over the last years. Recently, there are first indications that breast cancer incidence has started declining,” scientists in Lubeck, Germany report.
“We examined recent breast cancer incidence and actual data on HRT utilisation in Schleswig-Holstein, Germany, to find out population based evidence on decreasing breast cancer incidence and its possible relationship with reduced HRT usage. Breast cancer incidence is taken from the population based cancer registry of Schleswig-Holstein. HRT data was extracted from a cohort of 102,000 women taking part in a quality assurance project in breast cancer diagnosis for the years 2001-2005. The annual percentage change in incidence of breast cancer and HRT utilisation was measured by linear regression. There is a linear decline in HRT utilisation among less than 50 years group, 50-69 years group and all age group women between the years 2001 and 2005. Breast cancer incidence decreased between the years 2001 and 2005 for more than 50 years old and all age group, but not in the younger than 50 years women. The decline of breast cancer incidence started about two years after the HRT decline.!
Breast cancer incidence decline and decreased HRT utilisation showed a high correlation,” wrote A. Katalinic and colleagues, University of Lubeck.
The researchers concluded: “A drastic change in age-incidence relationship in breast cancer has taken place, the change is likely to continue and in future it has to be monitored closely with HRT use and other possible explanations.”
Katalinic and colleagues published their study in Breast Cancer Research and Treatment (Decline in breast cancer incidence after decrease in utilisation of hormone replacement therapy. Breast Cancer Research and Treatment, 2008;107(3):427-430).
March 26th, 2008
Moss RW.
A Cancer Journal for Clinicians published a warning by Gabriella D’Andrea, MD, against the concurrent use of antioxidants with radiotherapy and chemotherapy. However, several deficiencies of the CA article soon became apparent, not least the selective omission of prominent studies that contradicted the author’s conclusions. While acknowledging that only large-scale, randomized trials could provide a valid basis for therapeutic recommendations, the author sometimes relied on laboratory rather than clinical data to support her claim that harm resulted from the concurrent use of antioxidants and chemotherapy. She also sometimes extrapolated from chemoprevention studies rather than those on the concurrent use of antioxidants per se. The article overstated the degree to which the laboratory data diverged in regard to the safety and efficacy of antioxidant therapy: in fact, the preponderance of data suggests a synergistic or at least harmless effect with most high-dose dietary antioxidants and chemotherapy. The practical recommendations made in the article to avoid the general class of antioxidants during chemotherapy are inconsistent, in that if antioxidants were truly a threat to the efficacy of standard therapy, antioxidant-rich foods, especially fruits and vegetables, ought also be proscribed during treatment. Yet no such recommendation is made. Furthermore, the wide-scale use by both medical and radiation oncologists of synthetic antioxidants (eg, amifostine) to control the adverse effects of cytotoxic treatments is similarly overlooked. In sum, this CA article is incomplete: there is far more information available regarding antioxidant supplements as an appropriate adjunctive cancer therapy than is acknowledged. Patients would be well advised to seek the opinion of physicians who are adequately trained and experienced in the intersection of 2 complex fields, that is, chemotherapeutics and nutritional oncology. Physicians whose goal is comprehensive cancer therapy should refer their patients to qualified integrative practitioners who have such training and expertise to guide patients. A blanket rejection of the concurrent use of antioxidants with chemotherapy is not justified by the preponderance of evidence at this time and serves neither the scientific community nor cancer patients. Integr Cancer Ther. 2006 Mar;5(1):63-82.
March 14th, 2008
The higher a woman’s oestrogen level, the more likely breast cancer will come back, according to new research. The new study reveals that women whose breast cancer came back had almost twice as much oestrogen in their blood than women who remained cancer-free.
“While this makes sense, there have been only a few small studies that have looked at the link between sex hormones in the blood and cancer recurrence,” says Cheryl Rock, Ph.D., a professor in the Department of Family and Preventive Medicine at the University of California, San Diego. “This is the largest study to date and the only one to have included women taking agents such as tamoxifen to reduce oestrogen’s effect on cancer growth.”
For the study, researchers used data from a larger study on dietary intervention for breast cancer. Study authors matched 153 participants whose cancer had recurred to 153 participants who remained cancer-free. The pairs were alike in terms of tumour type, body size, age, ethnicity and treatments used. All of these participants had their blood tested at the beginning of the study, when they were all cancer-free. Two-thirds of the participants were using tamoxifen.
Researchers report higher levels of oestradiol concentrations significantly predicted cancer recurrence. Oestradiol is a steroid hormone and the primary human oestrogen. Women whose cancer returned has more than double the amount of oestradiol compared to women who remained cancer-free.
“What the results mean for women who have already been treated for breast cancer is that they should do as much as they can to reduce oestrogen in their blood, such as exercising frequently and keeping weight down,” Dr. Rock said. “Taking anti-oestrogen drugs like tamoxifen may not completely wipe out the hormone’s effect in women who have high levels of oestrogen.”
Cancer Epidemiology, Biomarkers and Prevention, March 2008
March 11th, 2008
I was in my late 30s or early 40s before I was willing to call them lies. I think I had to reach a certain threshold of maturity, experience, and open mindedness to accept the lies as such. These are not white lies, largely innocent with no damage done to another person (damage to the liar is another matter). Some of these are frank lies, others are half-truths, and still others are statements meant to mislead or to convince the patient that only he/she is responsible for a decision.
The statements listed are not always lies, but too often they are. When there is a major unspoken reservation after one of these statements, it is my belief that it becomes a lie. Here are a few of the relatively common lies in medicine.
#1: We got it all. This is the king of all lies in cancer. It is not uncommon today for a cancer surgeon to tell a patient or family member triumphantly that we got it all. Although it is justified in some instances, for most carcinomas this is blatantly wrong and biologically impossible, since many carcinomas are systemic in nature and micrometastases remain in the patient even with clear surgical margins. It misleads the patient and family into thinking the patient is cured.
Surgeons who tell this lie defend themselves by saying, What I meant was that we got all of the tumor we could see at surgery, or, Of course, the patient will need chemotherapy for the remaining microscopic cancer.
So why didn’t he say that? I hear various explanations: No need to burden the family and patient at this time, or, You never know; I might have gotten it all. I had a patient once that…
This introduces the second great lie:
#2: You never know. When I made rounds with fellows and junior faculty and we were faced with a difficult diagnostic or therapeutic decision, I would ask each to give his or her opinion and to explain the choice. One junior faculty member back in the 1970s often chose what seemed to be an excess of additional diagnostic tests or images, and he often chose therapeutic options that had a next-to-zero chance of success. When his choice was challenged he would say, You never know, meaning this might be the one in a million case in which there is a useful or positive result.
It drove me nuts. I wanted to grab his lapels and shake him saying, Of course we can’t be positive about any action we take; this is biology and medicine about which we are woefully ignorant, but we must apply what we know to make the best reasoned choice we can. You are using sloppy logic and, even worse, you are lying to yourself and possibly to the patient as well. I never did show any emotion or grab his lapels (I would have later in my career).
Unfortunately, this lie is still used today, if not in so many words, or even with no words at all. The patient with the third or fourth recurrence is offered an ineffective therapy because, You never know, and the lie is compounded when there is a substantial financial incentive to give the therapy. A related big lie follows:
#3: I did it because the family insisted on more therapy. This is a common excuse for giving or doing something that is clearly not in the patient’s short- or long-term best interests. It is often excused by the confusion of the nature of patient choice and sound medical advice or practice. Patients and/or families should be participants in decisions so they may express the boundaries of action they are most comfortable with. But the doctor is duty bound to do the same.
To blame the family for highly questionable interventions is an abrogation of responsibility by the doctor. It is very hard to say no to a desperate patient or family; there are many difficult actions physicians face in the normal course of their days. Nobody said it would be easy.
#4: It’s your decision. This is a variant of the preceding lie. There is no question that doctors influence patients’ decisions. Doctors have biases that may be based on scientific data or a common standard of practice, and it may therefore be reasonable to make a strong recommendation.
But in some cases the bias is personal, such as wanting to get more patients on a clinical trial, to do more surgery, to increase revenues, or to avoid having to deal with a difficult patient. In these cases, how the choice is presented along with the enthusiasm and salesmanship of the doctor can make it far more unlikely that the patient will choose an alternative option, even when at the end of the explanation the doctor says, It’s your decision.
In a technical sense, it is indeed the patient’s decision to go forward, but the strong conviction of the doctor has severely reduced the patient’s degrees of freedom. As noted above, a strong recommendation is sometimes indicated, but when those instances are based on a personal preference or bias, one must be extra careful to balance the bias through information and transparency.
#5: He’s a good doctor. Patients require referrals to specialists and most often depend on their current physician to recommend one. Physicians usually refer to specialists that they know personally or know to be competent by experience or word of mouth. But they may refer a patient because the specialist is a golfing buddy or in the same building or a business partner. The specialist may be quite competent, but one must ask oneself the simple question: If the patients were members of my family, would I send them to this specialist?
Or when one tells the patient, She is a good doctor, does he really mean, She is a good enough doctor, or He can probably handle this case; it isn’t so complicated?
Referral relationships are fragile and are often influenced by non-medical issues. One must be diligent to avoid exposing patients to unnecessary risks in order to satisfy a social or business obligation.
Thus, while each of the above statements can be used honestly and justly, they are too often used for more negative and sometimes shameful reasons. The test is the motivation found when being honest with oneself and, at the very least, facing the fact when one is not.
Oncology Times:Volume 30(2)25 January 2008p 3-4
March 8th, 2008
…A recently study on the effects of long-term use of certain dietary supplements including vitamin E and folates on lung cancer risk reported these supplements do not reduce risk. Daniel Fabricant, Ph.D., vice president of scientific and regulatory affairs for the Natural Products Association, questioned the study’s methodology: “The study states that ‘supplemental vitamin E was not associated with an increased risk of NSCLC (nonsmall cell lung cancer).’ When analyzed by dose categories, vitamin E was only associated with an increased risk when modeled continuously. In its simplest terms, this result is a ‘virtual’ clinical result, not a real one. The use of modeling is to better design future trials, not draw solid conclusions on risk by any means. Additionally, the study goes on to say that ‘results show a possible U-shaped association, with subjects using a medium dose for 10 years having a decreased risk, whereas those using a high dose for 10 years showed an increased risk.’ This point was irresponsibly absent in the press releases. Finally, the researchers do not analyze the effect of supplemental vitamin E on the non-smoking group, so at what point does the risk get appropriately assigned to cigarette use?” says Fabricant. The report was published in the American Journal of Respiratory and Critical Care Medicine, Volume 177, pages 524-530.
March 8th, 2008
By M Zhang, X Liu, J Li, L He, D Tripathy
Cochrane Database of Systematic Reviews 2008 Issue 1
Date of Most Recent Substantive Amendment: 18 February 2007
Abstract
Background
Short term side-effects of chemotherapy include fatigue, nausea, vomiting, mucositis and myelosuppression or neutropenia. These occur during the course of treatment and generally resolve within months of completion of chemotherapy. A variety of Chinese medicinal herbs have been used for managing these side effects.
Objectives
To assess the effectiveness and safety of Chinese medicinal herbs in alleviating chemotherapy-induced short term side effects in breast cancer patients.
Search strategy
We searched The Cochrane Breast Cancer Specialised Register (15/02/2007), The Cochrane Central Register of Controlled Trials (CENTRAL); (The Cochrane Library 2006, Issue 4); MEDLINE (1966 to December 2006); EMBASE (1990 to December 2006); and Chinese Biomedical Literature (2006, Issue 4). A number of journals were hand searched.
Selection criteria
Randomised controlled trials comparing chemotherapy with or without Chinese herbs in women with breast cancer.
Data collection and analysis
Two authors independently extracted the data, which were analysed using RevMan 4.2. For dichotomous data, we estimated the relative risk. For continuous data, we calculated the weighted mean difference.
Main results
We identified seven randomised controlled trials involving 542 breast cancer patients undergoing or having recently undergone chemotherapy. All studies were conducted and published in China. We did not pool the results because few studies were identified and no more than two used the same intervention. All were of low quality and used CMH plus chemotherapy compared with chemotherapy alone.
CMH combined with chemotherapy showed no statistically significant difference for the outcomes of phlebitis and alopecia. Only one study showed an improvement in nausea and vomiting, and in fatigue. Three indicated an improvement in white blood cells in the group receiving CMH. Two showed an increase in percentage changes in T-lymphocyte subsets CD4 and CD8. One study showed a statistically significant difference for CMH in percentage changes in T-lymphocyte subsets CD3, CD4 and CD8. Two herbal compounds may have improved quality of life. One study reported that CMH may have some effect on reducing toxicity in liver and kidney, but differences were not statistically significant.
Authors’ conclusions
This review provides limited evidence about the effectiveness and safety of Chinese medicinal herbs in alleviating chemotherapy induced short term side effects. Chinese medicinal herbs, when used together with chemotherapy, may offer some benefit to breast cancer patients in terms of bone marrow improvement and quality of life, but the evidence is too limited to make any confident conclusions. Well designed clinical trials are required before any conclusions can be drawn about the effectiveness and safety of CHM in the management of breast cancer patients.
Plain language summary
Chinese medicinal herbs for the treatment of side-effects from chemotherapy in breast cancer patients
Chinese medicinal herbs (CMH) include any mixture of herbal compounds and decoction (the process by which herbs are boiled and remaining liquid used for health purposes), including the development of herbal formulae and injections, and capsules. Although CMH are used to counteract the side effects of chemotherapy (cancer treatment with chemical agents that are selectively destructive to malignant cells and tissues) in patients being treated for cancer, the evidence for their use for women with breast cancer has not been ascertained. The purpose of this systematic review was to evaluate the effectiveness and safety of CMH in alleviating chemotherapy-induced short term side effects for women either undergoing chemotherapy or having recently undergone chemotherapy. Short term side effects are those that occur during the course of the treatment and generally resolve within months of the completion of the therapy and affect up to 60% of patients.They include nausea and vomiting, mucositis (inflammation of the mucous membranes lining the digestive tract from the mouth down to the anus caused by chemotherapy); neutropenia (a decrease in white blood cells caused by chemotherapy); myelosuppression (a condition in which bone marrow activity is decreased, resulting in fewer red blood cells, white blood cells, and platelets), and fatigue (loss of energy and tirdness). This review found seven randomised studies involving 542 breast cancer patients addressing this question. These studies used six different herbal remedies to treat the side effects of chemotherapy, all used CMH plus chemotherapy as the intervention compared with chemotherapy alone. The results suggest that using Chinese herbs in conjunction with chemotherapy or CHM alone may be beneficial in terms of improvement in marrow suppression and Immune sytstem, and may improve overall state of quality of life. However, further trials are needed before the effects of TCM for people with breast cancer can be evaluated with any real confidence.There was no evidence of any harms of CMH.
February 26th, 2008
Survival in advanced cancer patients is directly related to nutritional status, and this (as well as immune status) can be influenced by administration of fish oil together with vitamin E. This is the conclusion of Greek research just published in the journal “Cancer”.
The researchers studied a group of 60 patients with advanced, generalised solid tumours, which were felt to be no longer responsive to conventional treatment.
The cancer patients were randomised into intervention and placebo groups, with a further control group of 15 healthy patients. In each cancer group there were an equal number of adequately nourished patients and malnourished patients (as judged by a combination of weight loss >10%, serum albumin <30 g/L, serum transferrin <2.0 g/L and Karnofsky performance status <60) .
Intervention: consisted of daily fish oil (18 capsules of MAXEPA each containing 170 mg EPA/115 mg DHA) together with 200 mg of vitamin E. Nutritional status and immune function were measured before and during intervention. Immune assessment included T cell sub-sets and cytokine
production.
Results: Prior to treatment, the ratio of T-helper cells to T-suppressor cells was significantly lower in malnourished cancer patients compared to well nourished ones. This was considerably improved after fish oilsupplementation (see table 1).
Table 1: CD4/CD8 ratio before and after fish oil/vitamin E supplementation
ACTIVE PLACEBO Signif.
Well n. Maln. Well n. Maln. (Well n. vs Maln.)
————————————————————————————————–
Before 1.75 1.21 1.82 1.23 p<0.05
Day 40 2.03 1.84 1.79 1.19 NS
————————————————————————————————–
p value NS 0.05 NS NS
(pre vs post)
Initially malnourished patients survived for a mean period of 213 days (±19), compared with 481 days (±35) for initially well nourished patients.
The most interesting finding was that the combined group of supplemented patients – both those who were initially well nourished and those who were malnourished – had a significant increase in survival compared with the placebo patients (p < 0.025: see table 2).
The longest survived group was the initially well-nourished patients who received the supplementation, whilst the shortest survived group were the initially malnourished patients who were given placebo.
Table 2: Patient cumulative survival
Suppl. Placebo
————————————————-
Day 180 75% 50%
Day 240 65% 30%
Day 360 55% 25%
p<0.025
(NB: values above are approximate and estimated from the graph in the original paper)
Ref: Cancer 82:395-402, 1998
February 26th, 2008
Serum levels of androgens and oestrogens were not related to risk for developing prostate cancer in initially healthy men.
During the past several decades, many hypotheses about prostate cancer etiology have gained wide support, including family history, genetics, and consuming a Western diet. Elevated androgen levels have long been considered a likely risk factor, and many studies have been conducted in an attempt to characterize this attribute. For example, the Prostate Cancer Prevention Trial (PCPT) — the results of which demonstrated a 25% lower rate of prostate cancer in men who were randomized to receive the 5-reductase inhibitor finasteride — was designed, in part, to determine whether elevated androgen levels were associated with higher risk for developing disease (N Engl J Med 2003; 349:215).
In an unusual research effort, investigators who had published prospective studies on prostate cancer risk and endogenous sex hormone concentrations were invited to join a collaborative group. Most investigators who were contacted agreed to participate; data were contributed from 18 prospective studies (3886 men with prostate cancer and 6438 controls), which represented 95% of data available worldwide. In these studies, blood samples were collected from healthy men who were then followed to identify those who developed prostate cancer. Laboratory analyses were performed on blood samples from patients with incident prostate cancer and from matched control subjects. Data, including patient characteristics and all lab variables, were analyzed in a conditional logistic regression that was stratified by study, age at recruitment (2-year age bands), and date of recruitment (single year).
No significant associations were found between serum concentrations of any androgen or estrogen and risk for prostate cancer. Additionally, no association was noted between risk for prostate cancer and concentrations of androstanediol glucuronide, androstenedione, dehydroepiandrosterone sulfate, estradiol, or free estradiol. Levels of sex-hormone binding globulin were significantly and inversely related to prostate cancer risk. No interstudy heterogeneity was found in the estimated trends for any hormone, and adjustment for potential confounders did not affect risk estimates.
Comment: The findings from this impressive collaborative effort provide an important addition to our understanding of prostate cancer aetiology. As editorialists note, “By confirming the lack of evidence to support an androgen–prostate cancer hypothesis, the study obliges the scientific community to move past a seductive, clinically relevant, and biologically plausible hypothesis and get on with the difficult task of exploring, analyzing, and characterizing modifiable risk factors for prostate cancer.”
Published in Journal Watch Oncology and Haematology February 19, 2008
February 20th, 2008
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