TEAM Study of Adjuvant Endocrine Treatment for Breast Cancer Reveals the Cost of Patient Non-compliance

The largest study in the world of treatments for post menopausal, hormone positive breast cancer has shown that patients who continue to take exemestane or tamoxifen do significantly better than patients who start to take one drug (or tamoxifen followed exemestane) but then stop.

Professor Cornelis van de Velde, principal investigator at the central data office for TEAM (tamoxifen exemestane adjuvant multinational) trial told Europe’s largest cancer congress, ECCO 15 – ESMO 34, the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress, September 20 – 24 in Berlin, Germany, that differences in compliance between the nine countries involved in the trial shed light on the role that it played in patient outcome.

In the Dutch/Belgian part of the TEAM trial, more patients were node positive compared to those in other countries (and were therefore at higher risk of recurrences), because the existing Dutch treatment guidelines (which have since been changed) indicated that only ‘high risk’ patients should receive chemotherapy, endocrine treatment or both. Yet despite this handicap, recurrences of breast cancer in The Netherlands and Belgium were 12% for patients using tamoxifen and 9% of patients using exemestane compared to 8% and 7% internationally. This is probably due to better compliance with treatment in The Netherlands, which was significantly better than in other countries.

“Across the whole study, up to a cut-off point of two years nine months, non-compliance amongst women on tamoxifen was 19.8% and 12.9% for women on exemestane. However, these percentages were considerably lower in the Dutch/Belgian part of the TEAM trial where non-compliance was 14% for tamoxifen and 9% for exemestane Patients who stopped study treatment (tamoxifen or exemestane) had significantly higher chance of a recurrence; the chance was between four and five times higher among this group than among those who continued their treatment. This underlines the need for good information for patients concerning the side-effects of drugs and treatment efficacy,” said Prof van de Velde, who is Professor of Surgery at the Leiden University Medical Centre (Leiden, The Netherlands) and President of the European Society of Surgical Oncology. Compliance with medication in the TEAM study was lower than in any previous study of adjuvant aromatase inhibitors.

The TEAM study is a randomised phase III clinical trial comparing the efficacy of the aromatase inhibitor exemestane versus the current “gold standard” treatment tamoxifen as adjuvant endocrine therapies for hormone sensitive early breast cancer in postmenopausal women. After two years nine months a total of 9,779 women had been included in the trial from nine countries: France (1230 patients), Germany (1480), Greece (211), Japan (184), The Netherlands (2753), Belgium (414), UK/Ireland (1275), and the USA (2232).

The trial was started in 2001 but in 2004, based on results from another trial (Intergroup Exemestane Study) that showed a significant survival advantage for patients on exemestane, the TEAM study was changed so that patients receiving tamoxifen were switched to exemestane after having been in the trial for between two and a half to three years. The results presented today relate to data on disease-free survival in patients on the trial for no longer than two years nine months and they focus particularly on issues of compliance in the Dutch/Belgian TEAM patients, as well as on side effects, and disease-free and overall survival across the whole of the study.

Prof van de Velde noted: “Adverse side effects were the main reasons why patients discontinued their treatment – about half of all patients who discontinued did so because of side effects. Out of all the patients in the study, 6.3% discontinued tamoxifen and 4.4% discontinued exemestane because of side effects."

Adverse side effects included heart, skin, hormonal, digestive, metabolic, neurological, muscle and skeletal problems. Exemestane was associated with significantly higher rates of arthralgia, carpal tunnel syndrome, diarrhoea and high cholesterol levels, but with significantly lower rates of hot flushes, vaginal bleeding and discharge, and thromboembolism than tamoxifen. Fractures and heart problems were similar between the two groups.

“The safety profile has been better for exemestane than for tamoxifen and I think this is a contributory factor to the lower discontinuation rates amongst the patients on exemestane,” Van de Velde said.

After two and three-quarter years of follow-up, among the women on exemestane there were 11% fewer cases of a local recurrence of the tumour, distant metastases, breast cancer in the other breast (contralateral breast cancer) and deaths occurring without a relapse of the disease,than among the women on tamoxifen (352 in the exemestane patients and 388 in the tamoxifen patients). There were no differences between the two groups for time to contralateral breast cancer or overall survival, and no unexpected safety issues were reported. Patients aged 70 or over and women with breast cancer that had spread to only one to three lymph nodes had a significantly better disease-free survival on exemestane than on tamoxifen.

“The current analysis covers a short period of time with relatively few deaths occurring and this makes it difficult to see significant differences between the two groups. However, the data from TEAM indicate that early use of exemestane in these high risk patients appears to be safe and a more effective endocrine treatment than tamoxifen for reducing breast cancer recurrence,” said Prof van de Velde. “The study is continuing and the next end point has already been reached, so that we now have enough events to conclude whether starting with tamoxifen and switching to exemestane is better or worse than starting with exemestane. These results will be presented at the San Antonio breast cancer symposium in December.”

For more information:

• Abstract no: 2BA. Presidential session, Tuesday 12.30-14.30 hrs CEST (Hall 1)

Also read these PubMed Abstracts:

• Fallowfield LJ, Bliss JM, Porter LS, Price MH, et al. Quality of life in the intergroup exemestane study: a randomized trial of exemestane versus continued tamoxifen after 2 to 3 years of tamoxifen in postmenopausal women with primary breast cancer. J Clin Oncol. 2006 Feb 20;24(6):910-7

Post-menopausal Early Breast Cancer Patients May Benefit From Switching to Exemestane After Two Years of Treatment with Tamoxifen

New research has found that switching post-menopausal women with early breast cancer to the drug exemestane (Aromasin®, Pfizer, USA) after two or three years of tamoxifen rather than keeping them on tamoxifen for five years improves the chance of remaining cancer free and reduces the risk of death for at least the next six years.

“These findings have confirmed that the strategy of switching to exemestane mid-way through the five-year tamoxifen treatment plan provides a clear and durable benefit for relapse and overall survival,” the study’s leader, Professor Charles Coombes, head of oncology at Imperial College in London, told Europe’s largest cancer congress, ECCO 15 – ESMO 34, the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress, September 20 – 24 in Berlin, Germany. “We found that six years after changing treatment, women who got exemestane were 18% more likely to remain disease free and were 14% less likely to die than those who stayed on tamoxifen.”

Breast cancer is the leading cancer in women, with 1.29 million cases diagnosed worldwide every year. About 75% of breast cancers are oestrogen-receptor positive, meaning that oestrogen plays in important role in promoting the growth. Such tumours are usually treated with anti-oestrogen drugs.

Tamoxifen, also known by the trade names Nolvadex, Istubal, and Valodex, is the oldest of these. The drug blocks the tumour’s ability to use oestrogen and is the standard treatment after surgery in women who have early-stage breast cancer. It is normally taken for five years.

Exemestane belongs to a newer class of anti-oestrogen drugs known as aromatase inhibitors, which interfere with the function of aromatase, an enzyme responsible for the production of oestrogen. Aromatase inhibitors are accepted as an alternative to tamoxifen for post-menopausal women, but the question of how best to use these drugs remains under investigation.

The study tested whether switching to exemestane after two or three years of tamoxifen was more effective in the long term than continuing with tamoxifen for the remainder of the five years of treatment. The results presented in Berlin update findings reported previously, providing evidence based on a longer follow-up to produce a more robust estimate of the strategy’s effect on survival and disease recurrence and give a clearer picture of the long-term side effects.

“Our earlier analysis, based on a shorter follow-up, had shown a clear relapse advantage but until now, the magnitude and duration of the overall survival benefit had been uncertain. These updated results show that the relapse improvement does not seem to diminish over time and have clarified that the survival advantage is robust and enduring.”

The study, which has the longest follow-up of any trial to date investigating the impact of switching from tamoxifen to an aromatase inhibitor, involved 4,724 postmenopausal women from 37 countries with oestrogen-receptor-positive or unknown receptor status breast cancer who had their tumours cut out and had remained disease free after two or three years on tamoxifen. About half continued with tamoxifen until they had completed a total of five years of treatment, while the other half were switched to exemestane for the remaining period of treatment. The women were followed for an average of 91 months.

The 18% improvement in disease-free survival is derived from a hazard ratio of 0.82, while the 14% improvement in overall survival is calculated from a hazard ratio of 0.86.

“Practice changed in many countries after our early findings were released in 2004, from using five years of tamoxifen to the current recommended treatment strategy of switching these patients to exemestane or another aromatase inhibitor after two or three years of tamoxifen. The issue that has yet to be clarified is whether starting with tamoxifen and then switching is better than starting with an aromatase inhibitor,” Coombes said.

Cancer Research UK and Pfizer Ltd., which makes exemestane, funded the study.

For more information:

• Abstract no: 5010. Breast Cancer proffered papers session, Tuesday 09.00-11.00 hrs CEST (Hall 1)

Also read these PubMed Abstracts

• Eisen A, Trudeau M, Shelley W, Messersmith H, Pritchard KI. Aromatase inhibitors in adjuvant therapy for hormone receptor positive breast cancer: a systematic review. Cancer Treat Rev. 2008 Apr;34(2):157-74. Epub 2007 Dec 31. Review.
• Spicer J, Ellis P. Towards optimal endocrine therapy for hormone-sensitive breast cancer: initial versus sequential adjuvant aromatase inhibition.
  Cancer Lett. 2007 Apr 1 8;248(2):165-74. Epub 2006 Aug 21. Review.

Effective Cancer Drugs May Increase Risk of Adverse Effects, Report Says

Three drugs, including tamoxifen, reduce a woman's chance of getting breast cancer, but each drug carries distinct potential harms of its own, according to a new report from HHS' Agency for Healthcare Research and Quality.

Drugs to reduce the risk of breast cancer can be prescribed to women with a family history of breast cancer or other risk factors, but prescribing practices vary widely. The comparative effectiveness review found that all three drugs, tamoxifen (Nolvadex®; an antagonist of the estrogen receptor in breast tissue), raloxifene, (Evista; an estrogen agonist/antagonist, commonly referred to as a selective estrogen receptor modulator or SERM that belongs to the benzothiophene class of compounds), and tibolone (Xyvion; a synthetic anabolic steroid with estrogenic, androgenic and progestagenic activities), significantly reduce invasive breast cancer in midlife and older women but that benefits and adverse effects can vary depending on the drug and the patient.

"Taking medicine to avoid breast cancer in the first place is an attractive notion, but the decision to do so must be made by patients in consultation with their clinicians with benefit of the best evidence available," said AHRQ Director Carolyn M. Clancy, M.D. "These drugs are not necessarily for everyone. This report sheds important light on their advantages and potential harms."

The report is the first to make a direct, comprehensive comparison of the drugs so that women and their health care providers can assess the medications' potential effectiveness and adverse effects. The report compares the use of the three drugs to reduce the risks of getting breast cancer in women who have not previously had breast cancer.

Breast cancer is the second most commonly diagnosed cancer of women (after skin cancer), with more than 190,000 new cases diagnosed each year in the United States. It is estimated to cause more than 40,000 deaths per year. The National Cancer Institute estimates that nearly 15 percent of women born today will develop breast cancer in their lifetimes. Most cases of breast cancer occur in women with no specific risk factors other than age and gender, although family history of breast and ovarian cancer is associated with higher risk.

Tamoxifen, a selective estrogen receptor modulator (SERM), was approved by the U.S. Food and Drug Administration in 1998 to prevent breast cancer in women at high risk of developing the disease. Tamoxifen's use to reduce the risk of breast cancer is accepted clinical practice, although the drug is primarily used for treatment rather than risk reduction.

The AHRQ report compared tamoxifen with another SERM, raloxifene, which is primarily used to prevent and treat osteoporosis and was approved by the FDA for breast cancer risk reduction in 2007. A third drug, tibolone, which has not been approved by the FDA for use in the United States but is commonly used in other countries to treat menopausal symptoms and osteoporosis, also was included in the study.

The report found that all three drugs reduce the occurrence of breast cancer but have various side effects. The most common side effects for tamoxifen are flushing and other vasomotor symptoms (e.g., night sweats, hot flashes), vaginal discharge and other vaginal symptoms such as itching or dryness; for raloxifene, side effects include vasomotor symptoms and leg cramps; and for tibolone, side effects include vaginal bleeding.The report also found that each drug carried the risk of adverse effects. It found that tamoxifen increases risk for endometrial cancer, hysterectomies, and cataracts compared with the other drugs. Tamoxifen and raloxifene increase risk of blood clots, although tamoxifen's risk is greater. Tibolone carries an increased risk of stroke.

The report also examined the drugs' effectiveness and harms based on such factors as age, menopausal status, estrogen use, and family history of breast cancer and sought to identify the kinds of women who might be good candidates for prevention therapy, although the evidence is limited in this area. The report called for more research to more clearly identify characteristics of patients who would benefit from these drugs while suffering the least harm.

AHRQ's new report, Comparative Effectiveness of Medications to Reduce Risk of Primary Breast Cancer in Women, is the latest analysis from the Agency's Effective Health Care Program. That program, authorized by the Medicare Prescription Drug Improvement and Modernization Act of 2003, represents an important federal effort to compare alternative treatments for health conditions and make the findings public. The program is intended to help patients, doctors, nurses, and others choose the most effective treatments.

For more information:

• National Cancer Institute: Study of Tamoxifen and Raloxifene (STAR) Trial

PubMed abstracts:

• Cummings SR, Ettinger B, Delmas PD, Kenemans P, et al. The effects of tibolone in older postmenopausal women. N Engl J Med. 2008 Aug 14;359(7):697-708
• Escande A, Servant N, Rabenoelina F, Auzou G, Kloosterboer H et al. Regulation of activities of steroid hormone receptors by tibolone a.... J Steroid Biochem Mol Biol. 2009 Aug;116(1-2):8-14. Epub 2009 Apr 2.

Reduction in Breast Density Predicts Potential Benefit of Tamoxifen

A reduction in breast density appears to be one of the strongest indicators of a woman’s response to tamoxifen (Nolvadex®, Istubal®, Valodex®, AstraZeneca, 15 Stanhope Gate , W1K 1LN, United Kingdom), an orally active selective estrogen receptor modulator (SERM) that is used treat and to decrease breast cancer risk. This is one of the conclusions of a study by a team of British researchers led by Jack Cuzick, Ph.D., the study’s lead investigator and head of the Cancer Research UK Centre for Epidemiology, Mathematics and Statistics in London, United Kingdom, presented at the 31 Annual CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) in San Antonio, Texas (December 10 – 14, 2008).

The result of this study may lead to a re-evaluation of the importance of breast density, which is far the most undervalued and underutilized risk factor for breast cancer. Commenting on the study, Cuzick said that ‘Apart from age and BRCA1 and BRCA2 mutations, increased breast density is the leading risk factor for breast cancer.’

Density is a factor
Because of the differences in tissue composition and differences in the radiographic attenuation properties of fat, stroma, and epithelium, mammographic appearance of the breast varies among women.

In a study published in the January 2004 edition of Radiology, the journal of the Radiological society of North America, Dr Jennifer A. Harvey, MD and Dr Viktor E. Bovbjerg, PhD of the Departments of Radiology and Health Evaluation Sciences, of the University of Virginia in Charlottesville say that a plausible explanation of the association of breast density with increased breast cancer risk is the development of premalignant lesions such as atypical ductal hyperplasia, levated growth factors, or increased estrogen production within the breast due to overactive aromatase. The amount of breast density may also be due in part to genetic heredity.

Harvey and Bovbjerg noted that, unlike other risk factors, breast density may be influenced. 'Because breast density is very hormonally responsive, it may be influenced by lifestyle factors such as alcohol intake and diet,' Harvey explained. 'Breast density may reflect increased risk due to other causes or it may be an independent risk factor,' she continued. While weight, body mass index, age, menopausal status, age at first birth, nulliparity, family history, hormone use, and previous breast biopsy may all influence breast density, it is consistently identified as an independent risk factor after adjustment for other variables associated with both density and breast cancer risk

A number of studies in varied settings and populations have shown that women with dense tissue in 75% or more of the breast have a risk of breast cancer four to six times as great as the risk among women with little or no dense tissue. Based on this and other observations, Dr Karla Kerlikowske, MD, of the University of California in San Francisco, suggested, in an editorial in the January 2007 edition of the New England Journal of Medicine, that breast density should be measured in clinical practice and used to maximize primary and secondary prevention of cancer.

A Biomarker
However, for mammographic density to be considered as a biomarker, it is necessary to demonstrate that the risk reduction induced by a preventive intervention can be predicted by change in density, and that patients experiencing the largest change are most likely to benefit from treatment. Cuzick said that if their findings are validated in follow-up studies, women at risk for developing breast cancer should have a baseline mammogram before starting use of tamoxifen, and then a follow-up scan a year or two later to monitor breast density.

‘If there is a reduction, the agent is having an effect; if density is the same, it may not be a beneficial drug for the individual woman,' Cuzick noted. ‘It is important to find a way to predict who will respond to tamoxifen, and changes in breast density may constitute an early indicator of benefit,' he continued. ‘This is important to know because other preventive options now exist or are being tested.’

IBIS-1 and tamoxifen
Cuzick also led the International Breast Intervention Study I (IBIS-I), an international trial in which postmenopausal women at high risk of breast cancer were given tamoxifen to see how effective this drug is in preventing them from developing the disease. This trial involved more than 7,000 participants.

‘In the IBIS-1 study, tamoxifen reduced the risk of breast cancer by about 40%,’ Cuzick explained. In this study, we focus on whether the change in breast density after 12-18 months of prophylactic treatment predicts the subsequent impact of tamoxifen on the development of breast cancer.

Results of this study found the agent reduces the risk of estrogen-positive (ER) breast cancer by 30 to 40% among women at high risk. During that study, researchers collected baseline mammograms, as well as mammograms at 18, 36, and 54 months to check for breast cancer development. Based on analysis of these mammograms, Cuzick and his colleagues later found a strong correlation between reduction of breast density in women who use tamoxifen and lowered breast cancer risk. But for the rest of the women - where tamoxifen did not reduce breast density – risk of the disease was not significantly reduced.

In this follow-up study, the investigators examined a subpopulation of the IBIS-I participants (120 women who developed breast cancer and 943 who didn’t), to see if their mammograms changed over time and if tamoxifen treatment reduced breast density. They also looked at changes in other variables, such as hormone status, body weight and familial factors. They found that only change in mammographic density predicted reduction of risk for ER-positive breast cancer.

Confirmation required
For the 46 percent of women in the tamoxifen-treatment group whose breast density was reduced by 10 percent or more, the risk of breast cancer was reduced by 52 percent relative to the control group (women who did not develop breast cancer). Conversely, the 54 percent of women whose density was not reduced by 10 percent only had a non-significant, 8 percent reduction in breast cancer risk. The findings suggest that the impact of tamoxifen on risk reduction is predictable by changes it induces on breast density after 12 to 18 months of treatment, Cuzick said.

Although these findings need confirmation in an independent study, based on this data, Cuzick and his team concluded that changes in breast density may constitute an early indicator of treatment efficacy, which would be useful for the evaluation of new chemoprevention therapies. They also believe that by measuring density changes between baseline and initial follow up mammograms in high-risk patients receiving tamoxifen, it may be possible to determine which women are actually benefiting from the intervention (and should therefore continue treatment), and those who might benefit more from alternative risk reducing strategies.

A step towards personalized medicine
Researchers at the Cancer Research UK Cambridge Research Institute recently discovered the mechanism by which tamoxifen operates in breast cancer patients and how some women build up resistance to the drug.

Dr Lesley Walker, PhD., Cancer Research UK's director of cancer information, said: ‘Tamoxifen has been a huge success story helping to prevent breast cancer recurring for many women. Understanding why it occasionally stops working is really important because it allows us to identify new targets for drug development and who will need such treatments.’

Commenting on the importance of this study, she added: ‘We are moving into an era of personalised medicine and now, Professor's Cuzick's work has increased our knowledge of which high risk women will benefit from tamoxifen as a preventative drug, and which women won't benefit. This is a key advance as we try to ensure women get the most suitable treatment.’

For more information, read:

• Cuzick J, Warwick J, Pinney L, Warren R, et al. Change in breast density as a biomarker of breast cancer risk reduction; results from IBIS-1. (General Session 6) Abstract 61 San Antonio Breast Cancer Symposium. Contact the author.

For additional information:

• Understanding Cancer Series: Estrogen Receptors/SERMs (National Cancer Institute)
• Nolvadex® full prescribing information

Also read PubMed abstracts:

• Cuzick J, Forbes JF, Sestak I, Cawthorn S, et al. Long-term results of tamoxifen prophylaxis for breast cancer--96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst. 2007 Feb 21;99(4):272-82.
• Poweles TJ, Ashley S, Tidy A, et al. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst. 2007 Feb 21;99(4):283-90 Contact the author.
• Boyd NF, Guo H, Martin LJ, Sun L, et al. Mammographic density and the risk and detection of breast cancer. N Engl J Med. 2007 Jan 18;356(3):227-36. Contact the author. Full text article (PDF).
• Kerlikowske K. The mammogram that cried Wolfe. N Engl J Med. 2007 Jan 18;356(3):297-300.
• Vachon CM, van Gils CH, Sellers TA, Ghosh K et al. Mammographic density, breast cancer risk and risk prediction Breast Cancer. Res. 2007;9(6):217. Contact the author.
• McCormack VA, dos Santos Silva I. Breast density and parenchymal patterns as markers of breast cancer risk: a metaanalysis. Cancer Epidemiol Biomarkers Prev 2006;15:1159-69 Contact the author.
• Boyd NF, Rommens JM, Vogt K, et al. Mammographic breast density as an intermediate phenotype for breast cancer. Lancet Oncol 2005;6:798-808.
• Harvey JA, Bovbjerg VE. Quantitative assessment of mammographic breast density: relationship with breast cancer risk. Radiology 2004;230:29-41 Contact the author. Full text article.
• Ursin G, Ma H, Wu AH, et al. Mammographic density and breast cancer in three ethnic groups. Cancer Epidemiol Biomarkers. Prev 2003;12:332-8.
• Byrne C, Schairer C, Brinton LA, et al. Effects of mammographic density and benign breast disease on breast cancer risk (United States). Cancer Causes Control 2001;12:103-10.
• Duncan JA, Reeves JR, Cooke TG. BRCA1 and BRCA2 proteins: roles in health and disease. Mol Pathol. 1998 Oct;51(5):237-47.
• Boyd NF, Byng JW, Jong RA, et al. Quantitative classification of mammographic densities and breast cancer risk: results from the Canadian National Breast Screening Study. J Natl Cancer Inst 1995; 87:670-5.
• Byrne C, Schairer C, Wolfe J, et al. Mammographic features and breast cancer risk: effects with time, age, and menopause status. J Natl Cancer Inst 1995;87:1622-9.
• Wolfe JN, Saftlas AF, Salane M. Mammographic parenchymal patterns and quantitative evaluation of mammographic densities: a case-control study. AJR Am J Roentgenol 1987;148:1087-92.

Reduction in Breast Density Predicts Potential Benefit of Tamoxifen

Reduction in breast density appears to be a strong indicator of a woman’s response to tamoxifen, an agent used to decrease breast cancer risk. Increased breast density is the leading risk factor for breast cancer, apart from age.

At the CTRC-AACR San Antonio Breast Cancer Symposium, the British researchers said that if their findings are validated in follow-up studies, women at risk for developing breast cancer should have a baseline mammogram before starting use of tamoxifen, and then a follow-up scan a year or two later to monitor breast density.

If there is a reduction, the agent is having an effect; if density is the same, it may not be a beneficial drug for the individual woman, said the study’s lead investigator, Jack Cuzick, Ph.D., head of the Cancer Research UK Centre for Epidemiology, Mathematics and Statistics in London.

“It is important to find a way to predict who will respond to tamoxifen, and changes in breast density may constitute an early indicator of benefit,” said Cuzick. “This is important to know because other preventive options now exist or are being tested.” Cuzick led the International Breast Intervention Study I (IBIS-I), a trial of tamoxifen for breast cancer prevention that involved more than 7,000 participants. Results of the study found the agent reduces the risk of estrogen-positive (ER) breast cancer by 30 to 40 percent among women at high risk. During that study, researchers collected baseline mammograms, as well as mammograms at 18, 36, and 54 months to check for breast cancer development. Based on analysis of these mammograms, Cuzick and his colleagues later found a strong correlation between reduction of breast density in women who use tamoxifen and lowered breast cancer risk.

In this study, the investigators examined a subpopulation of the IBIS-I participants (120 women who developed breast cancer and 943 who didn’t), to see if their mammograms changed over time and if tamoxifen treatment reduced breast density. They also looked at changes in other variables, such as hormone status, body weight and familial factors. They found that only change in mammographic density predicted reduction of risk for ER-positive breast cancer.

For the 46 percent of women in the tamoxifen-treatment group whose breast density was reduced by 10 percent or more, the risk of breast cancer was reduced by 52 percent relative to the control group (women who did not develop breast cancer). Conversely, the 54 percent of women whose density was not reduced by 10 percent only had a non-significant, 8 percent reduction in breast cancer risk. The findings suggest that the impact of tamoxifen on risk reduction is predictable by changes it induces on breast density after 12 to 18 months of treatment, Cuzick said.

For more information:
Cuzick J, Warwick J, Pinney L, Warren R, Cawthorn S, et al. Change in breast density as a biomarker of breast cancer risk reduction; results from IBIS-1. Abstract 61; SABCS, December 10-14, 2008.