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Gold, incentives and meh

PMETB ‘delays’


Tired of wading through endless journals? Overwhelmed by too much evidence? In this series GPwSIs cut papers that will change the way they practise down to the bare bones. This month Dr Nick Brown looks at papers on cancer that have caught his eye

5 questions answered

1 What is the latest evidence on the link between hormone replacement therapy and breast cancer?

2 Was my cancer caused by stress, Doctor?

3 Hot flushes after breast cancer treatment: what can be done?

4 Does faecal occult blood testing have any role in the surveillance of patients who are already known to be at high risk of bowel cancer?

5 Is there any role for prophylactic antibiotics in patients receiving chemotherapy?

What is the latest evidence on the link

between hormone replacement therapy

and breast cancer ?


Paper one: Coombs NJ, Taylor R, Wilcken N, Boyages J. Hormone replacement therapy and breast cancer; estimate of risk. BMJ 2005 331:347-9

Method: This is a paper describing the derivation of absolute risk of HRT. Working from a population incidence on the use of HRT based on existing data from the latest quinquennial Australian Health Survey and

comparing this to the annual incidence of breast cancer, the authors calculate the attributable factor for HRT as a cause of breast cancer for each age group, using a previously described method.

Results: The average baseline life-time risk of developing breast cancer at age 40 is 7.2 per cent (1 in 14), reducing to 6.1 per cent (1 in 16) at age 50, and 4.44 per cent (1 in 25) at age 60. On average HRT was started at age 50 and oestrogen-only HRT has a minimal effect on the risk of breast cancer even with extended use, increasing the risk 0.2 per cent with five years' use and doubling this additional risk with every five years of additional use. The breast cancer risk is increased significantly with combination HRT, increasing by 0.6 per cent with five years' use and doubling it again for each additional five years. Once HRT is stopped the risk quickly returns to baseline levels and the accumulative absolute risk of breast cancer also returns to that of baseline levels.

Paper two: Chen W, Petitti DB, Geiger A.M. Mortality following development of breast cancer while using oestrogen, or oestrogen plus progestin: a computer record-linkage study. Br J Cancer 2005 93:392-398

Method: This study linked information on the patients first diagnosed with invasive breast cancer between 1993 and 1998 in California, with outpatient pharmacy data from 1992 to 2000. The all-cause and breast cancer mortality was compared for matched patients who were either non-HRT users, oestrogen HRT users, or combined HRT users in the year prior to the breast cancer presentation.

Results: Combined HRT users had a lower all-cause mortality and lower breast cancer mortality than either non-users or oestrogen users, while oestrogen users experienced little or no benefit compared to non-users.

Study conclusions: Although combined HRT appears to slightly increase breast cancer risk when taken for prolonged periods after the age of 50, patients who develop breast cancer while on combined HRT appear to have a slightly better prognosis. This increased incidence risk and increased prognosis effect is not observed in oestrogen-only HRT users.

What I am going to do: The risks and benefits are small, particularly when compared to other factors such as family history. Patients who prefer to take HRT for their beneficial effects should be reassured about this.

Was my cancer caused by stress, Doctor?

Paper: Neilson NR, Zuo-Feng Zhang, Kristensen TS, Netterstrom B, Schnohr P, Gronbaek M. Self reported stress and risk of breast cancer: prospective cohort study. BMJ 2005 331:548-50

Method: This was a prospective cohort study of 6689 women participating in the Copenhagen City heart study who were asked about their perceived level of stress at baseline. The first-time incidence of primary breast cancer was recorded during 18 years of follow-up.

Results: During the follow-up 251 were diagnosed with breast cancer and after adjustment for confounders, women with high levels of stress had a significantly reduced hazard ratio for breast cancer (0.6), compared for women with low stress levels. Also, for each increase in stress level on a six point scale, an 8 per cent lower risk of primary breast cancer incidence was found.

Study conclusions: High endogenous concentrations of oestrogen are a known risk factor for breast cancer and it is possible that chronic stress may impair this oestrogen synthesis and explain a lower incidence of breast cancer in women with high stress. However, any such impairment of this normal bodily function would not generally be considered to be advantageous!

What I am going to do: Reassure women with primary breast cancer who ask me whether stress could have precipitated their cancer and inform my hard-pressed reception staff that their stressful job may be doing them a favour with regards to their cancer risk!

Hot flushes after breast cancer treatment: what can be done?

Paper: Pandya KJ, Morrow GR, Roscoe JA, Zhao H, Hickok JT, Pajon E, Sweeney TJ, Banerjee TK, Flynn PJ. Gabapentin for hot flushes in 420 women with breast cancer: a randomised double-blind placebo-controlled trial. Lancet 2005 366(9488): 818-24

Method: This was a randomised double-blind placebo-controlled multi-institutional trial to assess the efficacy of gabapentin in controlling hot flushes in 420 women with breast cancer. Women were randomly assigned to two groups: placebo, gabapentin 300mgs a day, or gabapentin 900mgs a day by mouth in three divided doses.

Results: Percentage decrease in hot flush severity score between baseline on weeks four and eight effectively were 21 per cent and 15 per cent in the placebo group; 33 per cent and 31 per cent in the group assigned gabapentin 300mgs, and was 49 per cent and 46 per cent in the group assigned gabapentin 900mgs. Only the higher dose

of gabapentin was associated with significant decreases in hot flush frequency and severity.

Conclusions: Gabapentin is effective in the control of hot flushes at a dose of 900mgs bd and should be considered for treatment of hot flushes in women with breast cancer, for whom HRT may be considered unadvisable.

What I am going to do: Consider the use of gabapentin as an alternative to the other non-hormonal treatments for hot flushes that are already available such as clonidine and the anti-depressants fluoxetine, paroxetine and venlafaxine.

Does faecal occult blood testing have any role in the surveillance of patients who are already known to be at high risk of bowel cancer?

The paper: Bampton PA, Sandford JJ, Cole SR, Smith A, Morcom J, Cadd B, Young GP. Interval faecal occult blood testing in a colonoscopy based screening programme detects additional pathology. Gut 2005 54:803-806

Method: 1641 patients already enrolled within a regular colonoscopy surveillance programme were invited to have a FOB test. Any positive FOB was followed up by an additional colonoscopy and these colonoscopy results were analysed.

Results: 785 out of the 1641 patients invited had a FOB test; 57 of these patients tested positive on FOB and 52 of these patients had an additional colonoscopy. A further 14

patients were found to have a significant neoplastic lesion (1.8 per cent of those participating).

Conclusion: A one-off FOB test within a colonoscopy-based surveillance programme had a participation rate of nearly 50 per cent and appeared to detect additional pathology in 1.8 per cent of those patients. Some 27 per cent of the patients who were then subjected to an additional colonoscopy were actually found to have an abnormality and the treatment of these patients could then be expedited.

The appropriate interval between the surveillance colonoscopies for those at increased risk of colorectal cancer remains in debate. Local gastroenterology departments are struggling to keep up with local demand for colonoscopies, often due to recruitment difficulties, and the requirements of the Cancer Plan and scheduled investigations are often being delayed. FOB tests can be used in such circumstances to screen these patients.

What I am going to do: I have a number of such patients who are waiting for outstanding colonoscopies. The local hospital has stopped doing FOB tests but this test can be usefully offered for these patients within a general practice setting.

Is there any role for prophylactic antibiotics in patients receiving chemotherapy?

The paper: Gafter-Gvilli A, Fraser A, Paul M, Leibovici L. Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients. Annals Internal Med 2005 142:979-995

Method: This is a meta-analysis of 95 trials performed between 1973 and 2004 comparing antibiotic prophylaxis, placebo or no intervention in afebrile neutropaenic patients. Some 52 of the trials specifically addressed quinolone prophylaxis.

Interestingly the majority of trials appeared to use full therapeutic doses ie ciprofloxacin 500 mg bd, ofloxacin 200 mg bd and norfloxacin 400 mg bd as opposed to the usual 25 per cent prophylaxis dose.

Results: Antibiotic prophylaxis significantly decreased the risk of death, compared with placebo or no treatment (relative risk 0.67), although all prophylactic antibiotics were associated with an increased risk for adverse effects (relative risk 1.69). Quinolones such as ciprofloxacin were particularly effective, reducing all cause mortality by about half compared to placebo, as well as reducing infection-related mortality and morbidity. Quinolone prophylaxis increased the risk for harbouring resistant bacilli but these results were not statistically significant.

Conclusions: Most of these trials involved patients with haematological cancer and this showed that antibiotic prophylaxis for neutropenic patients undergoing cytotoxic therapy reduces mortality, particularly when quinolones are used.

What I am going to do: Consider using ciprofloxacin antibiotic prophylaxis for neutropaenic patients receiving chemotherapy, particularly where they may have other apparent infection risk.

Nicholas Brown is honorary primary care cancer lead, Kennet and North Wilts PCT and

a GP in Chippenham, Wiltshire

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