Drinking Wine May Increase Survival Among Non-Hodgkin’s Lymphoma Patients

Pre-diagnostic wine consumption may reduce the risk of death and relapse among non-Hodgkin’s lymphoma patients, according to an epidemiology study presented at the American Association for Cancer Research 100th Annual Meeting 2009.

Xuesong Han, the first author of the abstract and a doctoral candidate at the Yale School of Public Health, said their findings would need to be replicated before any public health recommendations are made, but the evidence is becoming clearer that moderate consumption of wine has numerous benefits. “This conclusion is controversial, because excessive drinking has a negative social and health impact, and it is difficult to define what is moderate and what is excessive,” said Han. “However, we are continually seeing a link between wine and positive outcomes in many cancers.”

This study was the first to examine the link among patients with non-Hodgkin’s lymphoma. Han and her colleagues analyzed data about 546 women with non-Hodgkin’s lymphoma.

They found that those who drank wine had a 76 percent five-year survival compared with 68 percent for non-wine drinkers. Further research found five-year, disease-free survival was 70 percent among those who drank wine compared with 65 percent among non-wine drinkers. Beer and/or liquor consumption did not show a benefit.

The study team at Yale also looked at subgroups of lymphoma patients, and found the strongest link between wine consumption and favorable outcomes among patients with diffuse large B-cell lymphoma. These patients had a 40 to 50 percent reduced risk of death, relapse or secondary cancer.

Researchers then conducted an analysis to examine the effect of wine consumption among those who had drunk wine for at least the previous 25 years before diagnosis. Non-Hodgkin’s lymphoma patients who had been drinking wine for at least this long had a 25 to 35 percent reduced risk of death, relapse or secondary cancer. Those patients with large B-cell lymphoma had about 60 percent reduced risk of death, relapse or secondary cancer if they had been drinking wine for at least the previous 25 years before diagnosis. “It is clear that lifestyle factors like alcohol can affect outcome,” said Han.

Reference

American Association for Cancer Research. (2009, April 24). Drinking Wine May Increase Survival Among Non-Hodgkin’s Lymphoma Patients. ScienceDaily. Retrieved July 6, 2016 from www.sciencedaily.com/releases/2009/04/090421154322.htm

Why is the Progesterone/Oestrogen Ratio So Important?

The levels of different molecules within tumour cells yield information about cancer’s nature – and in breast cancer, one of the most crucial for helping guide treatment is the oestrogen receptor (ER). Women with high levels of this molecule in their cancer cells (called ‘ER-positive’ breast cancer) benefit from hormone therapy – drugs that either lower their oestrogen levels, or prevent cancer cells responding to the hormone. About 7 out of ten women have ER-positive breast cancer.

ER-positive Breast Cancer.

But there’s a second molecule – the progesterone receptor (PR) – levels of which inside breast cancer cells also seem to be important.  Doctors have known for a long time that women with high levels of both the oestrogen and progesterone receptors (‘double-positive’) have the best chance of surviving – they respond better to treatment, and their cancer is less likely to spread. But these ‘double-positive’ women are given the same hormone therapy as those who have no progesterone receptor in their breast cancer, so doctors don’t always routinely test for this second molecule any more.

Until now, it’s been unclear why having high levels of both molecules is good news for the patient, or what benefit testing for progesterone brings.

But thanks to Cambridge-based Cancer Research UK researcher Dr Jason Carroll and his team, and their colleagues at the University of Adelaide in Australia, there are finally answers to this mystery. Today, they’ve published surprising results of a study in the journal Nature that finally solves the puzzle of why ‘double-positive’ women do better. And if their findings are confirmed in follow-up studies, it could make a big difference to how women are treated.

How do the ER and PR receptors work?

Only certain types of cells that respond to hormones make these receptors – for example breast, ovary and womb cells. Both receptors are directly involved in switching genes on and off – they’re called transcription factors. When oestrogen and progesterone are present, these hormones physically stick to their respective receptor, causing them to move into the nucleus of the cell, where DNA is housed. They can then attach to specific regions of our DNA and turn genes on or off, changing the cell’s behaviour.

When breast cancer develops, the tumour cells become overly sensitive to oestrogen. When oestrogen activates the oestrogen receptor, it turns on a panel of genes that tell the cells to keep dividing, driving tumour growth:

But what happens when breast cancer cells have a working progesterone receptor too? 

The first piece of the jigsaw fell into place when they looked at the physical relationship between the two receptors. Using ‘double-positive’ breast cancer cells grown in the lab, they made sure the cells had sufficient oestrogen and progesterone to activate both receptors, then they cracked the cells open.

When they used a sophisticated method to ‘fish out’ the progesterone receptor from the resulting mixture, they discovered something unexpected: it was physically stuck to the oestrogen receptor. This was a strong hint that progesterone – via the progesterone receptor – was somehow affecting how the oestrogen receptor works.

Using the same lab-grown breast cancer cells exposed to oestrogen only, the researchers used cutting-edge technology to pinpoint the sites in the cells’ DNA where activated oestrogen receptor attached – hence which genes it was controlling.

But when the scientists then added progesterone to the cells too, it caused a rapid shift in the points where oestrogen receptor attached to DNA.

At least 470 genes were controlled differently when both hormones were present compared to just oestrogen alone – the progesterone receptor was, in effect, ‘reprogramming’ the oestrogen receptor, changing the genes that it influences.

But, most crucial part was the overall effect this on the cancer cells themselves – progesterone seemed to cause the cells to stop growing as quickly.

By changing the genetic ‘programme’, the progesterone receptor was applying the brakes to the cells’ growth.

The cells used in the above experiments are based on tissue samples taken many decades ago, and kept artificially growing in a lab (called ‘cell lines’). These are a good starting point, but it was important to show this ‘ER reprogramming’ actually happens in human disease.

So the team turned a special technique developed by scientists in Professor Wayne Tilley’s laboratory at the University of Adelaide in Australia. This allowed small samples of tumour tissue to be removed from women with breast cancer and grown in the lab for a short time. Remarkably, the team saw exactly the same effect – adding progesterone at the same time as oestrogen slowed down the rate tumours grew.

They also saw exactly the same phenomenon in mice transplanted with human breast cancer cells: oestrogen fuelled tumours’ growth, but progesterone put the brakes back on.

The final, and most crucial, experiment was to see if their findings had any potential implications for treating breast cancer.  Again working with mice transplanted with tumour samples and given oestrogen, the researchers used the standard treatment for hormone-responsive breast cancer – tamoxifen, which slowed down tumour growth.

But when they gave the mice tamoxifen AND progesterone, the tumours grew even more slowly.

Changing the way breast cancer is treated? Dr Carroll’s research is a big step forward in understanding the role of progesterone receptor in breast cancer. Until now, its presence was simply considered an indication of how good a woman’s chances of surviving were.

But Dr Carroll’s study findings reveal that the receptor itself is the direct reason why these women have a better outlook.

Understanding the progesterone receptor’s role as a molecular handbrake on oestrogen-fuelled growth could also explain the observation that breast cancers frequently evolve to get rid of their progesterone receptors – this is an advantage to cancer, helping it grow quicker.

This new research offers a unique opportunity to exploit the braking action of the receptor with hormone therapy to improve breast cancer outcomes. According to Dr Carroll, this is precisely what needs to be done, and the next steps are obvious.

“The results are pretty clear and potentially have direct benefits for many women with breast cancer,” he told us.

“We’re already discussing a clinical trial to test whether giving women with ER/PR double-positive breast cancer progesterone, alongside oestrogen-blocking drugs, helps more women survive this disease”. If proven successful, they suggest that it could benefit up to half of women diagnosed with the disease.

Reference

Mohammed H. et al. Progesterone receptor modulates estrogen receptor-? action in breast cancer, Nature (2015), DOI: 10.1038/nature14583

Management of lymphedema related to breast cancer

Breast cancer–related lymphedema is an ongoing challenge for many survivors. A variety of treatments are available for the management of lymphedema, but the evidence supporting them varies. Complex decongestive therapy is a common treatment for lymphedema; however, the evidence supporting it is weaker than that supporting exercise.   Physicians can play a pivotal role as educators by informing breast cancer patients about the risk of secondary lymphedema, prevention strategies, early signs and symptoms, and treatment options. Evidence shows that early intervention is the key to effective treatment. Physicians can also help their patients by referring them to trained health care providers such as physiotherapists or lymphedema therapists.   Exercise prescription and compliance Lower incidences of lymphedema were found in women who exercised regularly, received lymphedema education before treatment, and performed preventive self-care activities (Park et la., 2008). Bani et al (2007) found that provision of education on lymphedema was associated with use of lymph-drainage massage services. Other factors associated with lower lymphedema incidence and severity included chemotherapy and antiestrogen drugs (Vignes et al., 2007).   Two main treatments were identified in the literature for the management of breast cancer–related lymphedema: complex decongestive therapy (CDT)—also known as combined decongestive therapy and complex decongestive physiotherapy—and exercise. Complex decongestive therapy has 4 components: manual lymphatic drainage (MLD); compression therapy; remedial arm and shoulder exercises; and deep-breathing exercises to promote venous and lymphatic flow (Koul et al., 2007).   Source Canadian Family Physician December 2010 vol. 56 no. 12 1277-1284 http://www.cfp.ca/content/56/12/1277.full   References Bani HA, Fasching PA, Lux MM, Rauh C, Willner M, Eder I, et al. Lymphedema in breast cancer survivors: assessment and information provision in a specialized breast unit. Patient Educ Couns 2007;66(3):311-8. Koul R, Dufan T, Russell C, Guenther W, Nugent Z, Sun X, et al. Efficacy of complete decongestive therapy and manual lymphatic drainage on treatment-related lymphedema in breast cancer. Int J Radiat Oncol Biol Phys 2007;67(3):841-6. Park JH, Lee WH, Chung HS. Incidence and risk factors of breast cancer lymphoedema. J Clin Nurs 2008;17(11):1450-9. Vignes S, Arrault M, Dupuy A. Factors associated with increased breast cancer-related lymphedema volume. Acta Oncol 2007;46(8):1138-42.

Dietary total antioxidant capacity is inversely associated with prostate cancer aggressiveness in a population-based study

A study by Vance et al., (2016) was to determine the relationship between total antioxidant capacity (TAC) from diet and supplements and prostate cancer aggressiveness among 855 African Americans (AA) and 945 European Americans (EA) in the North Carolina–Louisiana Prostate Cancer Project (PCaP). Cases were classified as either high aggressive, low aggressive, or intermediate aggressive. TAC was calculated from the vitamin C equivalent antioxidant capacity of 42 antioxidants measured via food frequency questionnaire.
EA reported greater dietary TAC from diet and supplements combined (P < 0.0001). In both minimally and fully adjusted logistic regression models, TAC from diet and supplements combined was associated with a reduced odds of high aggressive prostate cancer in all men, AA and EA: odds ratios for highest vs. lowest level (>1500 vs. These associations did not appear to differ between AA and EA. These data suggest that greater intake of antioxidants is associated with less aggressive prostate cancer.

Source
Nutrition and Cancer. DOI: 10.1080/01635581.2016.1134596

Visceral obesity is associated with poor prognosis in pancreatic adenocarcinoma

An association between obesity and unfavorable outcomes for various types of malignancy has been established. Nevertheless, the impact of visceral obesity (VO) on outcomes in pancreatic cancer is still unknown and controversial. The aim of this study was to uncover an association between VO and pancreatic cancer outcomes. We retrospectively reviewed 499 patients with pancreatic cancer who were diagnosed and treated in Severance Hospital from January 2006 to December 2011. Compared to the low-VO group, the high-VO group was mostly male and was more likely to have current smoking status, current alcohol intake status and diabetes mellitus.
The progression free survival (PFS) and overall survival (OS) were found to be significantly shorter by the Kaplan-Meier method in the high-VO group than in the low-VO group. In addition, the higher percentage of visceral fat was correlated with more lymph node metastasis and shorter OS. In patients with pancreatic cancer, VO at the time of diagnosis is associated with negative outcomes, such as shorter PFS and OS.
Source
Kim B, Chung MJ, Park SW, et al. Nutrition and Cancer. 2016 DOI: 10.1080/01635581.2016.1134600