Friday 23 January 2009

A tea-break may help reduce breast cancer

Three Cups of Tea Daily Could Cut Breast Cancer Risk
Thursday, January 22, 2009


Study: Drinking three cups of tea daily could cut breast cancer risk in younger women.
Three cups of tea a day could help keep breast cancer at bay among younger women.

Researchers at the Moffitt Cancer Center in Florida discovered an increased intake of tea reduced the risk among ladies under the age of 50 by up to 37 percent.

The threat of another type of tumor, affecting the lobes deep inside the breast tissue, was cut by two thirds, the researchers said.

They compared the lifestyles of 5,000 women with breast cancer to a similar number without the disease.

Tea, particularly green tea, contains plant-based disease fighting polyphenols, which are believed to account for the cancer protection.

And that is not the only health benefits daily tea consumption brings.

Previous studies have found these to include a lower risk of heart attack and stroke, a lower cholesterol level and improved blood pressure management.

Wednesday 31 December 2008

Risk Factors for Breast Cancer

Here are a list of risk factors from the American Cancer Society. They are broken down into those that can (such as excessive alcohol use) and cannot be modified (such as age or family history)

Risk Factors for Breast Cancer

AI vs Tam - now or later? Update from the 2008 San Antonio Breast Conference

More evidence suggesting that aromatase inhibitors (AIs) have slightly better efficacy than tamoxifen (Tam) as adjuvant therapy for postmenopausal women with estrogen-receptor-positive (ER+) breast cancer was at the 31st Annual San Antonio Breast Cancer Symposium (SABCS) on December 17.

Both drug approaches reduce estrogen, but in different ways. Tamoxifen is a selective estrogen-receptor modulator (also called a SERM) that prevents estrogen from interacting with its receptor, whereas AIs act by inhibiting an enzyme involved in the synthesis of estrogen from androgen after the menopause, and hence reduce the level of the hormone interacting with its receptor.

Three AIs are currently marketed in Australia— letrozole (Femara, Novartis), anastrozole (Arimidex, AstraZeneca) and exemestane (Aromasin, Pfizer).
So far, various combinations of trials (giving an AI versus Tam for 5 years), giving Tam for 2-3 years and then “switching” to an AI or giving 5-years of an AI after 5 years of Tam have all shown that AI’s are slightly better in reducing relapse but survival gains have been relatively small.

Relapse free survival time is the measure of time between diagnosis and an “event”. These events include a new cancer in the opposite breast, disease coming back in the same breast (if breast conservation was undertaken) or the chest-wall (if a mastectomy was undertaken) or disease coming back elsewhere in the body. Many trials also include the appearance of a totally different cancer or dying from something unrelated to breast cancer as an “event”. A more robust end-point for assessing the benefit of anticancer drugs is overall survival (the time from diagnosis to death from any cause) or breast cancer mortality (the time from diagnosis until death from breast cancer).

Apart from relapse or survival, quality of life is also very important. Although the survival data are very similar between Tam and AI’s, the toxicity profiles are quite distinct, with great sexual morbidity for some women with the AIs and more joint pain and osteoporosis. This has to be balanced with a slightly higher risk of a blood clot (or “DVT”) or cancer of the womb (endometrial cancer) with Tam.


The meta-analysis that Dr. Ingle presented at the meeting was split into two cohorts:
Cohort 1 consisted of data from “monotherapy” clinical trials that directly compared an AI to tamoxifen (9586 patients with a median follow-up of 5.9 years).
Cohort 2 consisted of data from "switching" trials in which the patients on tamoxifen were switched to an AI after 2 or 3 years (9015 patients with a median follow-up of 3.9 years). Here’s the fine print from the abstracts:


Cohort 1: 9,856 pts with 50,000 woman-years of follow-up. At 5 yrs, AI therapy was associated with an absolute 2.7% (standard error [SE] 0.7) decrease in BC recurrence (10.7% vs 13.4%, relative decrease 20% [SE 5], p=0.00004). There appeared to be greater proportional decreases in isolated local recurrence (30% [SE 10], p=0.003) and in contralateral disease (38% [SE 12], p=0.003) than in distant recurrence (12% [SE 6], p= 0.04). AIs yielded an absolute 1.0% (SE 0.5) decrease in BC mortality (5.5% vs 6.5%, relative decrease 7% [SE 7], p=0.28. The difference was even less and about 0.5% at 8 years.


Cohort 2: 9,015 pts with 33,000 woman-years of follow-up. At 6 yrs from treatment divergence (i.e., 8-9 yrs from diagnosis), AI therapy was associated with an absolute 3.5% (SE 1.1) decrease in BC recurrence (12.6% vs 16.1%, relative decrease 29% [SE 6], p<0.00001). There appeared to be greater proportional reductions in isolated local recurrence (40% [SE 13], p=0.002) and in contralateral disease (35% [SE 16], p=0.03) than in distant recurrence (24% [SE 7], p= 0.001). AIs yielded an absolute 1.6% (SE 0.8) decrease in BC mortality (6.3% vs 8.0%, relative decrease 22% [SE 9], p=0.02). Subset analyses with respect to PgR status, age, tumor grade and nodal status revealed no apparent heterogeneity between the proportional reductions in recurrence and no indication of an increase or decrease in non-breast deaths with AIs in either cohort 1 or 2.


Very importantly non breast cancer mortality and overall mortality were not higher with the AIs in either cohort was reassuring regarding their overall safety.

My view is that any efficacy gain had to be balanced not only against tolerability for each patient but also the risk of recurrence and presence of other risk factors such as osteoporosis or a family history of thrombosis. If the risks of recurrence are low (e.g a strongly ER positive grade 2 tumour measuring under 15mm) then the benefit of an AI over Tam is miniscule at most. If the risk of recurrence is higher then I would tend to favour an AI. On the other hand if a woman is perimenopausal and I am not really sure if she has stopped ovulating it is safer to start off with Tamoxifen as AI’s can stimulate ovulation and cause an unwanted pregnancy. If a woman has a strong family history of blood clots or more rarely endometrial cancer then Ais are a better approach.

Tamoxifen is now available as a generic, so is much cheaper than the branded AIs. In Australia the the difference may be between $20 and $300, for Tam versus an AI. Of course there needs to be a return on the multiple millions of dollars invested by pharmaceutical companies testing and discovering new drugs but in many situations, such as poorer Pacific islands or countries without pharmaceutical reimbursement, Tam may be a much better option.

Although AIs carry the risk for osteoporosis, this can be monitored and countered with bisphosphonates. I usually recommend baseline blood levels of calcium, vitamin D and parathyroid hormone and organise a baseline bone density measure before we start AI’s. Many women are Vit D deficient and this can make matters worse for bone strength.

A good middle ground approach supported by this new metaanalysis is to start patients with Tam for 2-3 years which can maintain or indeed increase bone strength particularly in the younger perimenopausal woman where we may not be certain that ovulation has ceased. The switching data also show that there may be a small survival advantage.

A major question than remains, however, is how long such treatment should be continued. Studies are currently in progress, comparing 5 years of therapy with 10, and 10 years of therapy with 15. Certainly, for women at higher risk of relapse (say with positive nodes) it makes sense to continue treatment for at least 10-years for the moment based at least on the MA-17 trial which shows a survival advantage of 5-years of Femara after 5-years of Tam (2). Ultimately, each patient needs to be assessed almost on an individual basis based on her prognosis, psychology and side-effect questions.

References:
1. http://sabcs.org/
2. http://www.ncbi.nlm.nih.gov/pubmed/16730271

Tuesday 30 December 2008

Zoledronic Acid Significantly Reduced Relapse in Early Breast Cancer

A recent Austrian trial presented at the American Society of Clinical Oncology meeting in May 2008 showed that 4mg of Zoledronic Acid given twice a year significantly reduced relapse in early breast cancer.

Zoledronic acid is already marketed in Australia as Zometa by Novartis for use in the treatment of bone metastases.

Following surgery, women who had not reached the menopause were treated with the lutenizing hormone-releasing hormone (LHRH) agonist goserelin for ovarian suppression, combined with either the antiestrogen drug tamoxifen or the aromatase inhibitor anastrozole (Arimidex, AstraZeneca).

In addition, 1 group of women also received zoledronic acid (4 mg intravenously every 6 months). Treatment was continued for 3 years.

After a median follow-up of 5 years, there were 54 events in the zoledronic acid group and 83 events in the 2 goserelin groups (hazard ratio, 0.64; P = .015). This translates into a 36% reduction in the risk for disease progression, Dr. Gnant added. There was a significant reduction in locoregional disease progression (10 events in the zoledronic acid group vs 20 events in the 2 goserelin groups) and distant metastases, both bone and nonbone (29 events in the zoledronic acid group vs 41 events in the 2 goserelin groups).

None of the 1800 women in this study received adjuvant chemotherapy after their surgery and only 5% received it before their surgery. They all had hormone therapy.

At five years, 137 women (7.6%) had had a recurrence, while 42 (2.3%) deaths occurred. This means this study found a 98% chance of survival in young women who are given ovarian suppression and hormone therapy drugs but do receive any chemotherapy.

This is an importnat aspect of the study and certainly supports the view that many young women with small ER-positive may be being overtreated with chemotherapy.

Also, the study found that there was no difference between in recurrence risk in the women who took tamoxifen and those who took an aromatase inhibitor. This again is critically important as in my view, Tamoxifen is better tolerated in this age group with less sexual side-effects.


In the group that received Zometa, 39 had a recurrence and six developed contralateral breast cancer. In the group that did not received Zometa, 61 had a recurrence and 10 developed contralateral breast cancer. This was a statistically significant, 36% reduction in recurrence.

However, with zoledronic acid the most serious side effect is an increased risk of developing osteonecrosis of the jaw. The researchers monitored the women closely and no cases were seen as yet.

It's very important to note that this study was done in premenopausal women who were on hormone therapy to suppress ovarian function. The findings may not hold true for women who have had cehemotherapy or perhaps for women with hormone receptor negative cancers. We also don't know if the findings will be true for postmenopausal women.

For the moment we should keep an eye on this and other studies before we recommend it in routine practice but this is a good study worthy of a change in practice for selected patients.

The NCI in the US summarised this study

NCI report of Zoledronic acid study

Saturday 25 October 2008

Myths about breast cancer

Here's a news story from the Sydney Morning Herald on the 23rd October 2008 about the common myths regarding breast cancer.