Tamoxifen Legacy Lasts Long Term

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Janette
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Tamoxifen Legacy Lasts Long Term

Postby Janette » Sun Aug 21, 2011 9:39 pm

Tamoxifen Legacy Lasts Long Term

Research has confirmed that tamoxifen (brand name: Nolvadex) reduces the risk of breast cancer coming back (recurrence) during the standard 5 years of treatment and that recurrence risk stays lower during the next 5 years AFTER tamoxifen treatment ends.

The results were published online July 29, 2011 in the journal Lancet.

After surgery and other treatments (chemotherapy, radiation therapy) women diagnosed with early-stage, hormone-receptor-positive breast cancer usually take 5 years of a hormonal therapy medicine to lower recurrence risk. When hormonal therapy is used this way it's called adjuvant hormonal therapy.

Of the adjuvant hormonal therapy choices, tamoxifen has been approved the longest and is approved to treat both premenopausal and postmenopausal women. The other main type of hormonal therapy medicines are the aromatase inhibitors, which are approved to treat only postmenopausal women.

This study analyzed the long-term outcomes of more than 21,000 premenopausal and postmenopausal women in 20 studies comparing tamoxifen to placebo (sugar pill) to treat breast cancer. Nearly 10,650 of the women were diagnosed with hormone-receptor-positive breast cancer, the type of breast cancer tamoxifen is expected to treat.

A study that combines and analyzes the results of many studies is called a meta-analysis. The Early Breast Cancer Trialists' Collaborative Group (EBCTCG) did this meta-analysis.

Results showed that in women diagnosed with hormone-receptor-positive breast cancer, recurrence risk was 30% lower overall over 15 years in women who got tamoxifen for 5 years compared to women who got placebo for 5 years:

* Recurrence risk was 47% lower during years 1-4 of treatment in women who got tamoxifen compared to women who got placebo.
* Recurrence risk was 32% lower during the last year of treatment and the first 4 years after treatment stopped (years 5-9) in women who got tamoxifen compared to women who got placebo.

These very positive results on the long-term benefits of adjuvant tamoxifen come from studies that began more than 15 years ago. Tamoxifen continues to be the recommended adjuvant hormonal therapy for PREmenopausal women diagnosed with hormone-receptor-positive, early-stage breast cancer. The aromatase inhibitors have become the recommended adjuvant hormonal therapy for POSTmenopausal women diagnosed with hormone-receptor-positive, early-stage breast cancer.

Aromatase inhibitors are preferred over tamoxifen for postmenopausal women because a number of studies have shown that postmenopausal women treated with an aromatase inhibitor have a slightly lower recurrence risk than women treated with tamoxifen.

Tamoxifen and the aromatase inhibitors work in different ways to lower recurrence risk. Tamoxifen blocks the effects of estrogen on breast cancer cells. Aromatase inhibitors lower the amount of estrogen in the body. The aromatase inhibitors are:

* Arimidex (chemical name: anastrozole)
* Aromasin (chemical name: exemestane)
* Femara (chemical name: letrozole)

While the aromatase inhibitors are preferred over tamoxifen for postmenopausal women diagnosed with early-stage, hormone-receptor-positive breast cancer, factors such as side effects and cost may still make tamoxifen a better choice for some women.

Hot flashes and night sweats -- called vasomotor symptoms -- are side effects of both tamoxifen and the aromatase inhibitors, though they're more common with tamoxifen. Joint pain is a more common side effect of the aromatase inhibitors. Both tamoxifen and the aromatase inhibitors can cause serious side effects. Treatment with either tamoxifen or an aromatase inhibitor can lead to dangerous blood clots in rare cases. This complication is more common with tamoxifen. Also, aromatase inhibitors can weaken bones and make women more likely to break a bone.

Tamoxifen, Arimidex, and Femara are available as generic medicines, so these may be less expensive than Aromasin (depending on your insurance coverage).

When choosing how to take an adjuvant hormonal therapy medicine, guidelines from The American Society of Clinical Oncology (ASCO) offer options for women and their doctors to consider:

* Take the same hormonal therapy for all 5 years (monotherapy).
* Take tamoxifen for 2 or 3 years and then switch to an aromatase inhibitor until hormonal therapy has been taken for a total of 5 years (sequential therapy).
* Take tamoxifen for 5 years if an aromatase inhibitor was started but had to be stopped before a full 5 years was completed, perhaps because of unacceptable side effects.

There is still a question about the value of continuing to take adjuvant hormonal therapy for more than 5 years. All the women in the meta-analysis took adjuvant hormonal therapy for 5 years. But other research results suggest that taking adjuvant hormonal for more than 5 years might make sense for some women.

ASCO guidelines recommend that most women take adjuvant hormonal therapy for a total of 5 years. Still, ASCO notes that some women may benefit from taking adjuvant hormonal therapy for 8 to 10 years (called extended adjuvant therapy). In these cases, ASCO recommends 5 years of tamoxifen followed by 3 to 5 years of an aromatase inhibitor.

If you're a postmenopausal woman who's been diagnosed with hormone-receptor-positive, early-stage breast cancer, keep two things in mind when you and your doctor are deciding on an adjuvant hormonal therapy plan:

* Every woman responds differently to treatment. What works for someone else may not work for you and what works for you may not work for someone else.
* Your treatment plan isn't written in stone. You can always switch medicines if another treatment has greater benefits and/or fewer side effects.

It's a good idea to ask your doctor about the differences in benefits and side effects between aromatase inhibitors and tamoxifen, as well as the pros and cons of monotherapy vs. sequential therapy. Together, you can decide on a treatment plan that's best for YOU.
Research News on Hormonal Therapy

(MedPage Today) -- The reductions in breast cancer recurrence and mortality seen with tamoxifen persist past the first decade, researchers found in a long-term analysis.

Treatment for about five years cut annual breast-cancer mortality by 30% throughout the first 15 years after the start of treatment (P<0.00001) across the 20 randomized trials pooled by the Early Breast Cancer Trialists' Collaborative Group.

Earlier benefits in terms of relapse appeared maintained beyond year 10, the group reported online in The Lancet.

That the curves didn't converge suggested true prevention that "potentially cures many patients," Stephen K. Chia, MD, of the British Columbia Cancer Agency in Vancouver, and Antonio C. Wolff, MD, of Johns Hopkins, commented in an accompanying editorial.

"These mature and definitive results allow clinicians to inform women confidently about the effect of tamoxifen on breast-cancer events and overall survival to a time point that approaches the remaining life expectancy of many individuals," they wrote.

Aromatase inhibitors are recommended for use by postmenopausal women at some point during adjuvant treatment of hormone-receptor positive breast cancer, although without the same kind of long-term evidence available for tamoxifen, Chia and Wolff noted.

The older drug remains a good option for women whose ovaries still function, though, they pointed out.

The meta-analysis showed no significant excess in uterine cancer or fatal pulmonary embolism risk with tamoxifen in women under age 55.

There were small absolute increases in both risks for women who started the drug between 55 and 69, but overall non-breast cancer mortality wasn't elevated (RR 1.02, P=0.79).

The patient-level meta-analysis included 10,645 women with estrogen receptor-positive breast cancer among the more than 21,000 early-stage breast cancer patients in 20 trials that randomized women to about five years of tamoxifen or placebo.

Recurrence rates fell 47% with tamoxifen compared with placebo in the first four years of follow-up and 32% from years five to nine (both P<0.00001), then stabilized without further comparative gain or loss through year 14.

For all-cause mortality, though, each period showed additional reductions, with benefits of tamoxifen continuing to accrue at 10 years and beyond (RR 0.73, P<0.00001).

The absolute mortality advantage with tamoxifen rose from 3% at the end of five years of treatment (9% versus 12%) to 9% by year 15 (24% versus 33%).

The risk reductions seen with tamoxifen appeared largely independent of progesterone receptor expression and nodal status of the original tumor, the patients' age, and receipt or timing of chemotherapy.

Estrogen receptor (ER) expression was the one factor that strongly predicted tamoxifen's benefits.

Patients with ER levels below 10 fmol/mg cytosol protein showed no impact from tamoxifen in the meta-analysis.

But any higher level of expression predicted "substantial" reduction in risk of recurrence, from a risk ratio of 0.67 at a weakly positive 10 to 19 fmol/mg to 0.52 at 200 fmol/mg or higher (P=0.002 for trend).

A sharp cutoff in the advantage by ER level isn't biologically plausible, Chia and Wolff noted.

"Therefore, another crucial message from this update is the need for accurate and sensitive immunohistochemistry assays to detect even low concentrations of ER and thus further identify potential candidates for adjuvant tamoxifen treatment," their editorial said.

Few ER-positive tumors have less than 10% of cells stain positive but the American Society of Clinical Oncology defines positivity with as few as 1% staining positive, and those tumors shouldn't be missed, the editorialists argued.

The next key issue to resolve is whether more than five years of endocrine therapy would boost outcomes further for breast cancer survivors, they noted.

Early Breast Cancer Trialists' Collaborative Group is funded from CRUK, BHF, and MRC core support of CTSU, which also performs trials funded by industry grants to the University of Oxford.

Primary source: The Lancet Source reference: Early Breast Cancer Trialists' Collaborative Group "Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials" Lancet 2011; DOI: 10.1016/S0140-6736(11)60993-8.Additional source: The LancetSource reference: "With maturity comes confidence: EBCTCG tamoxifen update" Lancet 2011.
Janette


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