The Lance Armstrong Foundation (LAF) announced that Mary Robinson, the first female President of Ireland and former United Nations High Commissioner for Human Rights, will serve as Honorary Chairperson of the LIVESTRONG Global Cancer Summit. The Summit, to be held in Dublin, Ireland August 24-26, 2009, is the landmark event of the LIVESTRONG Global Cancer Campaign, an initiative to address the burden of cancer worldwide. The Summit will bring together world leaders, non-governmental organizations, corporate leaders and individuals who are making new commitments to cancer control.

“I have always viewed healthcare as a fundamental issue of human rights. It is estimated that about one-third of cancers can be cured if detected and treated early,” said Robinson. “It is up to all of us — governments, non-governmental organizations, cancer survivors, all concerned individuals — to see that detection and treatment are offered to as much of the world’s population as possible. Through the LIVESTRONG Global Cancer Summit we will make great strides towards making this a reality.”

Lance Armstrong Foundation President and CEO Doug Ulman said, “Mary Robinson embodies the LIVESTRONG spirit of selfless service and leadership for the sake of positive change in our world. She has been a tireless advocate for issues at the intersection of health and human rights throughout her career — and we share the view that cancer control is at its core an issue of human rights.”

The LIVESTRONG Global Cancer Summit will make the case for urgent action to address the global cancer burden and introduce new commitments for cancer control by bringing together world leaders, corporations, non-governmental organizations and advocates in an unprecedented show of solidarity. Australian Prime Minister Kevin Rudd, Mexican President Felipe Calderon Hinojosa and former U.S. President Bill Clinton are included in the list of leaders expressing support for the Campaign and Summit, along with the Irish government and the Irish Cancer Society. The LAF is also in ongoing conversations with the Kingdom of Jordan and representatives of other nations about substantial new commitments.

Commitments are critical to avoid a looming public health catastrophe. Cancer kills more people every year than AIDS, tuberculosis and malaria combined. It is estimated that cancer will be the leading cause of death worldwide by 2010. However, many governments devote few resources to fighting cancer and collect little information about its causes and effects. The LAF is working with world leaders to focus on developing international partnerships, cancer advocacy, research and data collection.

“In 2010, cancer will be the leading cause of death worldwide. The LIVESTRONG Global Cancer Summit is an invaluable opportunity to stand up for the 28 million cancer survivors worldwide and to create a unified effort to control cancer through new commitments to action. This is not just a job for governments and medical researchers — it’s everyone’s job,” Ulman said.

The secondary purpose of the Summit is to build a global grassroots advocacy movement to influence global action in the fight against cancer. Participation in the Summit is by invitation only. LAF has outlined a commitment process that all world leaders and representatives from non-governmental organizations and corporations are required to complete to be eligible for invitation. For more information about the LIVESTRONG Global Cancer Campaign or the commitment process, visit http://www.LIVESTRONG.org.

Following its successes in Australia, California and Mexico, the LIVESTRONG Global Cancer Campaign will head to Europe for the Giro d’Italia (May 9-31), the Tour de France (July 4-26), the Tour of Ireland (Aug. 19-23) and the LIVESTRONG Global Cancer Summit in Ireland (Aug. 24-26), as well as other locations to be announced soon.

About the Lance Armstrong Foundation

At the Lance Armstrong Foundation, we fight for the 28 million people around the world living with cancer today. There can be — and should be — life after cancer for more people. That’s why we kick in at the moment of diagnosis, giving people the resources and support they need to fight cancer head-on. We find innovative ways to raise awareness, fund research and end the stigma about cancer that many survivors face. We connect people and communities to drive social change, and we call for state, national and world leaders to help fight this disease.

A prevention program serving an ethnically diverse population of women at high risk of cancer is detailed in an article published Monday 23 March in the online peer-reviewed journal ecancer.

The article describes a screening program to identify women from underserved communities who are at a high risk of developing breast or ovarian cancer; a pilot clinical research initiative sponsored by The Lynne Cohen Cancer Screening and symposium Project for High Risk Women.

Despite the advances in cancer diagnosis, treatment, and survival, racial and ethnic minorities suffer disproportionately from cancer. Ethnic and racial minorities are often less likely to take part in screening programs than Caucasian patients.

The pilot project will constitute the core of a broad-based screening program in New York City and, ultimately, a world class Clinical service targeted to women at high risk for cancer, in particular, women of minority ethnic groups.

Dr Franco M. Muggia, Director of Medical Oncology at NYU’s Langone medical Center will conduct the study at the Kaplan Cancer Center facilities. At Bellevue Hospital, the advanced services will be offered to 75 to 100 women who do not have access to normal medical screenings. Women referred to the program will receive state-of-the-art preventive care and early detection screening.

“Following a detailed family and personal history intake and physical exam, each woman on their initial visit is categorised into low (standard), high, and indeterminate risk groups. Women found to be at high risk of developing breast and/or ovarian cancer were referred for further testing, additional screening measures, or participation in chemoprevention trials” states Muggia.

Often women will not undergo screening procedures because of economic concerns, this program however, is completely free.

Continued and sustained efforts are needed on all fronts (education, practice, and research, policy) to improve the poor cancer-related outcomes for ethnic minorities.

Author:

Franco Muggia: Division of Medical Oncology, NYU Langone Cancer Institute, New York, NY 10016, USA.

ecancer is the online open-access peer-reviewed journal from the European Institute of Oncology in Milan, Italy.

A new metal nanostructure developed by researchers at the University of California, Santa Cruz, has already shown promise in cancer therapy studies and could be used for chemical and biological sensors and other applications as well.

The hollow gold nanospheres developed in the laboratory of Jin Zhang, a professor of chemistry and biochemistry at UCSC, have a unique set of properties, including strong, narrow, and tunable absorption of light. Zhang is collaborating with researchers at the University of Texas M. D. Anderson Cancer Center, who have used the new nanostructures to target tumors for photothermal cancer therapy. They reported good results from preclinical studies earlier this year (Clinical Cancer Research, February 1, 2009).

Zhang described his lab’s work on the hollow gold nanospheres in a talk on Sunday, March 22, at the annual meeting of the American Chemical Society in Salt Lake City.

“What makes this structure special is the combination of the spherical shape, the small size, and the strong absorption in visible and near infrared light,” Zhang said. “The absorption is not only strong, it is also narrow and tunable. All of these properties are important for cancer treatment.”

Zhang’s lab is able to control the synthesis of the hollow gold nanospheres to produce particles with consistent size and optical properties. The hollow particles can be made in sizes ranging from 20 to 70 nanometers in diameter, which is an ideal range for biological applications that require particles to be incorporated into living cells. The optical properties can be tuned by varying the particle size and wall thickness.

In the cancer studies, led by Chun Li of the M. D. Anderson Cancer Center, researchers attached a short peptide to the nanospheres that enabled the particles to bind to tumor cells. After injecting the nanospheres into mice with melanoma, the researchers irradiated the animals’ tumors with near-infrared light from a laser, heating the gold nanospheres and selectively killing the cancer cells to which the particles were bound.

Cancer therapy was not the goal, however, when Zhang’s lab began working several years ago on the synthesis and characterization of hollow gold nanospheres. Zhang has studied a wide range of metal nanostructures to optimize their properties for surface-enhanced Raman scattering (SERS). SERS is a powerful optical technique that can be used for sensitive detection of biological molecules and other applications.

Adam Schwartzberg, then a graduate student in Zhang’s lab at UCSC, initially set out to reproduce work reported by Chinese researchers in 2005. In the process, he perfected the synthesis of the hollow gold nanospheres, then demonstrated and characterized their SERS activity.

“This process is able to produce SERS-active nanoparticles that are significantly smaller than traditional nanoparticle structures used for SERS, providing a sensor element that can be more easily incorporated into cells for localized intracellular measurements,” Schwartzberg, now at UC Berkeley, reported in a 2006 paper published in Analytical Chemistry.

The collaboration with Li began when Zhang heard him speak at a conference about using solid nanoparticles for photothermal cancer therapy. Zhang immediately saw the advantages of the hollow gold nanospheres for this technique. Li uses near-infrared light in the procedure because it provides good tissue penetration. But the solid gold nanoparticles he was using do not absorb near-infrared light efficiently. Zhang told Li he could synthesize hollow gold nanospheres that absorb light most efficiently at precisely the wavelength (800 nanometers) emitted by Li’s near-infrared laser.

“The heat that kills the cancer cells depends on light absorption by the metal nanoparticles, so more efficient absorption of the light is better,” Zhang said. “The hollow gold nanospheres were 50 times more effective than solid gold nanoparticles for light absorption in the near-infrared.”

Zhang’s group has been exploring other nanostructures that can be synthesized using the same techniques. For example, graduate student Tammy Olson has designed hollow double-nanoshell structures of gold and silver, which show enhanced SERS activities compared to the hollow gold nanospheres.

The ability to tune the optical properties of the hollow nanospheres makes them highly versatile, Zhang said. “It is a unique structure that offers true advantages over other nanostructures, so it has a lot of potential,” he said.

Source: Tim Stephens
University of California – Santa Cruz

The National Health Service (NHS) cancer plan for England shows some beneficial effect on survival, although wide regional variations remain; more follow-up data are needed before the true impact of the cancer plan can be fully established. These are the conclusions of the first study to assess whether the cancer plan is working, published in an Article Online First and in the April issue of The Lancet Oncology.

In an accompanying Reflection and Reaction comment, Karol Sikora (CancerPartnersUK) states that, despite the tripling of investment in cancer care in the UK over the past decade, these findings show that there has been no striking improvement in cancer survival. According to a Leading Edge editorial published with the Article by The Lancet Oncology, the evidence shows that: “We are at best keeping track with improvements elsewhere rather than closing the gap.” The editorial adds that the cancer plan’s stated aim – of having five year cancer survival rates comparable with the best in Europe by 2010 – is looking optimistic.

In 2000, when the NHS cancer plan for England was introduced, Britain had one of the poorest levels of cancer survival in Europe. The plan was designed to improve 5-year survival rates for cancer, so they would compare with the best in Europe by 2010. In Wales there was no comparable cancer initiative until 2006, thus providing an opportunity to compare survival trends in England and Wales and assess the effectiveness of the English cancer plan.

In this study, Michel Coleman from the Cancer Research UK Cancer Survival Group London School of Hygiene and Tropical Medicine in London, UK, and colleagues report the national and regional survival trends in 2•2 million adults diagnosed with 21 common cancers in England and Wales and followed up to 2007. They analysed trends in short-term survival for patients diagnosed before the cancer plan (1996-2000), during initialisation (2001-03), and after implementation (2004-06).

Overall, 1-year survival* improved for most cancers in England and Wales between 1996 and 2006. Findings showed a slightly faster improvement in 1-year survival in Wales than in England between 1996 and 2003, but this was reversed after 2004 when annual trends in survival were more favourable in England than in Wales. For cancers of the stomach, colon, rectum, uterus, ovary, and kidney, survival trends in England improved after 2001, even without screening or the widespread use of effective new treatments. By contrast, bladder cancer, Hodgkin’s lymphoma, and leukaemia all showed a fall in survival.

However, differences in 3-year survival patterns between England and Wales were less obvious, with no difference in survival trends at 3 years or more for patients diagnosed up to 2003, and slightly faster increase in survival in England than in Wales between 2001-03 and 2004-06.The authors also note continued wide regional variation in survival, with more affluent southern regions having generally higher survival than the average survival for England.

They suggest that the improvements in survival trends in England since 2004 might be related to the cancer plan, but caution that it is not known whether the various initiatives in the cancer plan were fully implemented by that time. They conclude by calling for detailed analysis of the effect of more specific measures in the cancer plan, such as shorter waiting times and the creation of multidisciplinary teams, on cancer survival.

Mike Richards, the National Cancer Director for England, questions whether Wales is an appropriate control group for assessing progress in England in a second accompanying Reflection and Reaction comment. He points out that both countries took very similar approaches to cancer control by implementing cancer strategies that have worked at different times. He suggests that the differences in trends between the countries in 2001-03 and 2004-06 reflect Wales moving forward faster in the earlier years as a result of the Cameron report in 1996, and survival improving more quickly in England after 2000 as a result of the cancer plan.

Sikora also argues that the modest improvement in survival is because of: “a whole system fault within the NHS with serial delays, poor access and serious under-capacity.” He concludes: “We need to derive value from cancer services by increasing access and quality but not cost”. The Lancet Oncology editorial concludes that: “Perhaps the time has come to consider rather more fundamental changes to the NHS than are offered in the cancer plan if England is to truly offer world-class healthcare.”

*1-year survival can be considered to reflect early or late diagnosis of cancer, and 3-year and 5-year survival to reflect both early diagnosis and the effect of treatment.

Tony Kirby
Press Officer
The Lancet
32 Jamestown Road
Camden
London
NW1 7BY

http://www.thelancet.com

In the current issue of ONCOLOGY, Hershman and Shao provide a comprehensive review of anthracycline-induced cardiotoxicity (AIC). Risk factors for AIC include age (??18 or ??65 years) at time of treatment, increasing cumulative dose or dose intensity of anthracyclines, mediastinal radiation therapy (RT), and female gender.[1-4] The Surveillance, Epidemiology and End Results (SEER)-Medicare database showed that women older than age 65 who received nonanthracycline chemotherapy did not experience significant incremental cardiotoxicity compared to age-matched controls, but among the women who received anthracyclines, an excess rate of congestive heart failure emerged.[5]

Classification of Anthracycline-Induced Toxicity
As described by Hershman and Shao, AIC can be categorized as three distinct types: acute, early, and late. Acute AIC, occurring during the anthracycline infusion or within 1 week of therapy, is rare and reversible. It may present as transient arrhythmia, a pericarditis-myocarditis syndrome, or acute failure of the left ventricle.[6-8] Delayed AIC typically presents as a cardiomyopathy and has been reported in approximately 5% of patients.[9,10] It is classified as early subacute cardiotoxicity occurring < 1 year or late cardiotoxicity occurring > 1 year after the cessation of chemotherapy.[11] Late cardiotoxicity may not be apparent until years to decades after the administration of anthracyclines.[11,12] Patients typically have reduced left-ventricular mass, mass index, and ventricular compliance, with increasing susceptibility to cardiac stressors.[13] The majority of patients who develop early subacute cardiotoxicity will manifest late cardiotoxicity.[11,14]

While numerous studies have reported late AIC in patients exposed to the drug during childhood, the incidence in the adult population has been difficult to determine, as follow-up time and cardiac monitoring are inadequate in most clinical trials. Our group reported long-term AIC in 32 of 85 patients treated with sequential dose-dense and dose-intense doxorubicin, paclitaxel, and cyclophosphamide (ATC).[15] At a median follow-up of 7 years, the median absolute change in left-ventricular ejection fraction (LVEF), measured by multigated acquisition (MUGA) from baseline was 5.5%, and from the end of chemotherapy was ?2.0%. Four patients (12%) had an LVEF < 50%; two of the four patients had an LVEF < 50% at the end of chemotherapy. We concluded from this study that late asymptomatic decline in cardiac function is uncommon, and does not appear to significantly contribute to the morbidity or mortality of the regimen.

Monitoring of Cardiac Function
As Hershman and Shao note, echocardiogram (ECHO) and MUGA scans are standard methods used to monitor AIC. The authors refer to the limited applicability of MUGA scan for frequent monitoring as a result of cumulative radiation exposure; however, when a precisely reproducible measurement is required for patient management decisions or clinical trial monitoring, MUGA may be the method of choice.[16]

Serial MUGA assessments of LVEF vary between 2% and 4%, whereas serial ECHO assessments of LVEF vary between 13% and 17%. Several studies have reported a decrease in LVEF >?10 points from baseline or a fall below the institutional lower limit of normal as indicative of AIC.[17-20] However, such a drop is a late event and would not be detectable until significant cardiac damage has occurred.[21] Therefore, alternative methods of cardiac monitoring are being evaluated.

As described by Hershman and Shao, magnetic resonance imaging (MRI) is an alternative method used for assessment of myocardial function, perfusion, and tissue characterization. However, long-term data to support its use in this setting are lacking, especially with the limited availability of this technology.[22] Another modality under investigation is tissue doppler imaging (TDI), which allows the measurement of diastolic and systolic velocities of the ventricular walls and mitral annulus, and appears to be more reliable and less affected by loading conditions than conventional Doppler.[23] In a study by Tassan-Mangina et al, TDI confirmed the occurrence of early diastolic and late systolic impairment of left-ventricular function following moderate-dose anthracycline therapy.[23]

Hershman and Shao refer to troponin T and B-type natriuretic peptide (BNP) as potential biomarkers for earlier detection of cardiotoxicity. BNP levels were monitored for a small number of patients with acute leukemia treated with a daunorubicin-containing regimen; those who had abnormal BNP levels during subsequent stem-cell transplant developed heart failure, whereas those who had normal BNP levels did not.[24] Troponin levels were measured in 211 patients with breast cancer receiving high-dose therapy; abnormal levels predicted the development of future LVEF depression in a 12-month follow-up.[25]

Cardiac Risk Assessment and Management Recommendations
Although anthracyclines have served as the mainstay of effective cytotoxic therapy for breast cancer during the past 30 years, AIC remains a concern. Therefore, better methods for prevention, monitoring, and management of AIC are needed. When making treatment recommendations for breast cancer patients—especially those with early-stage disease—the presence of cardiac risk factors and strong cardiac family history need to be considered. Treatable cardiac risk factors such as hypetension, hyperlipidemia, and diabetes should be closely monitored and managed in an attempt to prevent additional cardiac injury.

In addition, long-term follow-up is needed to identify patients with subclinical late cardiac dysfunction, who may be at a higher risk for subsequent cardiac events. Patients with preexisting cardiac disease and poorly controlled risk factors may consider treatment with alternative non-anthracycline regimens with reported lower risk of cardiotoxicity.

As mentioned by Hershman and Shao, non-anthracycline-containing regimens have been evaluated for treatment of patients with early-stage breast cancer.[26,27] These non-anthracycline regimens appear to be comparable in efficacy and less cardiotoxic than the anthracycline regimens. While relatively short follow-up has been reported for these regimens, at very least they provide an alternative for breast cancer patients with a history of cardiac disease or cardiac risk factors. These nonanthracycline regimens should be discussed with patients as an alternative treatment, with acknowledgment of the relatively short duration of follow-up.

Finally, the potential for delayed cardiotoxicity should continue to be evaluated in adjuvant and neoadjuvant clinical trials, particularly in light of the recent advances with dose-dense therapy as well as with adjuvant trastuzumab (Herceptin).

Positron-emission tomography (PET) technology has drastically improved in the past few years, with the development of hybrid imaging devices combining PET and computed tomography (CT), which have essentially replaced stand-alone PET scanners in most centers. Image quality has also increased with the use of improved PET detectors and image reconstruction techniques. While a few years ago a “neck to thigh” PET scan could take as much as 90 minutes to complete, this procedure can now be performed in less than 15 minutes with modern instruments, leading to faster throughput and improved images. Due to well defined indications for many common malignancies such as lung cancer, colorectal carcinoma, and lymphoma, PET/CT imaging has become commonplace in many industrialized countries.

However, despite Medicare reimbursement in the United States for specific clinical settings, the clinical impact of PET/CT imaging has not been as significant in breast cancer as in other malignancies. In that context, the article by Almubarak, Osman, Marano, and Abraham provides a timely review of the topic. The authors essentially conclude that while the role of [18F]-fluorodeoxyglucose (FDG)-PET/CT imaging is limited in the initial diagnosis and staging of breast cancer, this modality can be useful in detecting suspected recurrence, assessing for distant metastases, and measuring treatment response to chemotherapy.

Importance of Early Detection
Breast cancer is a common cancer that will afflict one out of nine women during their lifetime. Although breast cancer has a high cure rate when detected early, metastatic breast cancer remains an incurable disease, which can be managed by a variety of relatively effective therapies, but with the eventual development of resistance and disease progression.

Mammography is credited with earlier detection and improved survival of women with breast cancer.[1] Because of the limited specificity of this test in some cases, many investigators are looking into second-line imaging techniques to avoid performing invasive procedures for diagnosis. Given the high accuracy and low morbidity of the various breast biopsy techniques, imaging tools would need to be highly accurate to influence management in this setting.

As pointed out by Almubarak and colleagues, PET imaging suffers from a lack of sensitivity for small breast tumors with a diameter less than 1 cm. In addition, some large tumors can be missed because of their low incorporation of FDG. Even relatively large lobular carcinomas and some estrogen receptor–sensitive breast cancers, for example, can sometimes have a very low FDG uptake,[2,3] and the sensitivity of FDG-PET imaging to detect axillary metastases with this histology is much lower than for invasive ductal carcinoma.[4]

Sensitivity vs Specificity
Conversely, since mammography is not highly sensitive either, tools such as magnetic resonance imaging (MRI) and positron-emission tomography (PET) have also been considered for screening high-risk women, particularly those with dense breasts. Although highly sensitive, MRI suffers from a lack of specificity, resulting in positive predictive values as low as 17% in this setting,[5] leading to many biopsies, which can create a strain on the capacity of breast imaging departments.

In this context, PET instruments with the capacity to detect very small tumors in the breast do exist (“positron emission mammography”).[6,7] However, given the close relationship between FDG uptake and tumor biology, as noted by Almubarak et al, it is possible and even likely that some breast cancers will be missed because of low FDG uptake.

An ongoing study scheduled for completion this year should provide further information on the potential benefits of this technology compared to MRI (clinicaltrials.org study #NCT00484614). Further studies are needed in this setting, and perhaps new radiopharmaceuticals will improve the accuracy of positron-emission tomography for the detection of primary breast cancer.

Role of PET
It is fair to say that at this stage, there is no clinical indication for the routine use of PET in the initial diagnosis of breast cancer. Due to its ability to evaluate breast tumor biochemistry, PET imaging may well provide additional prognostic data for women with breast cancer, but whether this information will be complementary or redundant to immunohistochemical findings and other molecular markers of poor prognosis from paraffin-embedded or frozen biopsy specimens remains to be established in the clinical setting.

Likewise, given the low morbidity and high accuracy of sentinel lymph node biopsy for the detection of axillary nodal metastases, there is no indication to perform PET or PET/CT imaging for axillary nodal staging. PET imaging is simply not sufficiently sensitive to detect nodal metastases in clinically negative axillae.[4,8] For detection of distant metastases in untreated patients, PET imaging is more accurate than other conventional imaging modalities, but the cost-effectiveness of using this procedure on a routine basis is not likely to be favorable.

PET/CT is perhaps best reserved for cases with equivocal conventional imaging results when the detection of distant metastases would alter management. PET/CT might be useful when selectively used in staging aggressive lesions such as triple-negative breast cancers, but further studies on this topic will be necessary. The uptake of FDG in primary tumors has been linked with tumor grade[2] and the presence of axillary or distant metastases.[9] Triple-negative tumors also tend to have higher FDG uptake.[10] A recent retrospective study conducted in women with inflammatory breast cancer showed that PET/CT imaging detected distant metastasis in 49% of cases, many of which were not detected by conventional staging.[11]

Troubleshooting Niche
There are certainly data in the literature to suggest that FDG-PET imaging is useful in restaging patients with a newly suspected recurrence based on clinical, laboratory, or radiologic findings. The detection of distant metastases in this setting can alter management, as local recurrence would be treated aggressively with surgery and/or radiation, whereas systemic treatment would be altered in the presence of metastatic disease.

Given the high clinical impact of PET imaging in the management of patients with recurrent breast cancer,[12] this tool fills a niche in troubleshooting many complex cases where recurrence is suspected clinically while conventional imaging remains negative or equivocal. Demonstrating this benefit in a prospective clinical trial remains difficult in light of the biologic heterogeneity of breast cancer and the number of treatment options that can be offered in various clinical scenarios. Although somewhat limited in high-quality prospective studies, current data support the selective use of PET/CT imaging in the diagnosis of recurrent breast cancer when the results are reasonably expected to affect clinical management.

Assessing Response to Therapy
PET imaging can provide faster assessment of disease response to therapy. A PET scan performed after three cycles of chemotherapy is predictive of survival, as shown in some studies in the neoadjuvant[13] and metastatic settings.[14] This approach may reduce unnecessary treatments that may carry the risk of significant toxicity despite limited benefits to women with resistant cancers. It may also provide a quick surrogate indicator of response in clinical trials for the evaluation of new drugs.

In clinical practice, whether interventions guided by PET imaging translate into improved outcomes—ie, reduced toxicity and/or improved survival compared to traditional clinical and conventional imaging response assessment methods—will remain debated until large scale, well designed prospective studies address this question.[8] The lack of a definite cure for metastatic breast cancer creates challenges in identifying measurable endpoints for the use of imaging techniques in patients who are likely to be subjected to multiple rounds of diverse diagnostic and therapeutic procedures over several years.

“Anastrozole is the only aromatase inhibitor (AI) which has now been shown to prevent recurrences in women with hormone receptor positive early breast cancer both during the initial high-risk two years after surgery, and also well beyond the completion of treatment. In breast cancer there are no guarantees and we can’t predict which women will experience a recurrence or when, so it is essential we have a treatment that has sustained efficacy against all types of recurrence that persists even after treatment is completed. If we can stop breast cancer returning, we can stop women dying from it.” – Professor Tony Howell, Christie Hospital, UK

Macclesfield, UK, Friday 13 March 2009: A new analysis of the ATAC (ARIMIDEX, Tamoxifen, Alone or in Combination) trial, presented today at the 11th International St Gallen Oncology Conference, Switzerland, shows that during the first two years after surgery, anastrozole is superior to tamoxifen at reducing the risk of breast cancer returning in postmenopausal women with hormone receptor positive early breast cancer (n=5,216).1 Anastrozole has consistently demonstrated superiority over tamoxifen, both during the five-year treatment period and beyond treatment completion.2 This latest analysis provides further reassurance that prescribing anastrozole from the start protects women in the crucial first two years when the risk of recurrence is highest, meaning that fewer patients have to be told the devastating news that their breast cancer has returned.

When breast cancer returns, particularly outside the breast at distant sites such as bone, liver or lung, it is no longer curable. Therefore protecting women from recurrence is the number one priority for doctors and is imperative to saving lives. Although the risk of recurrence can persist for up to at least 15 years,3 the risk is at its greatest within the first two years following surgery, as seen in the ATAC study where over half of all excess recurrences and deaths among patients taking tamoxifen occurred in the first two and a half years.2

This latest analysis confirms that in women who benefit from treatment with AIs (84% of the total ATAC population) anastrozole is even more effective at preventing all types of early recurrence (32%; 2 years post surgery) than previously seen in the broader study population (17%; 2.5 years post surgery).1

Professor Howell continued, “It is now standard practice to assess the hormone receptor status of breast tumours to guide the best course of treatment. ATAC is a ground breaking study which has led to a significant change in treatment strategies in breast cancer with aromatase inhibitors, such as anastrozole, now replacing tamoxifen as the standard of care for postmenopausal women with hormone receptor positive disease in many countries. These new findings confirm that in the women who receive it in routine clinical practice, anastrozole offers reassuring protection against their cancer returning at the time of greatest risk, giving women the best chance of continuing their lives cancer-free.”

The ATAC trial is one of the world’s largest and longest-running clinical studies in postmenopausal women with early breast cancer. With a median follow-up of 100 months – significantly longer than any other adjuvant AI trial – ATAC provides further information on the safety profile of anastrozole which remains predictable, with no long-term safety concerns. As a result of the weight of efficacy and safety evidence for anastrozole, it is now the most widely prescribed AI worldwide, with over twice as many prescriptions as the next most widely prescribed AI and over 4 million patient years’ experience.4 These new data will offer doctors treating hormone receptor positive postmenopausal early breast cancer further confidence that initial treatment with anastrozole offers women the best chance of staying recurrence free.

Anastrozole offers sustained protection against recurrence, demonstrating significantly superior disease free survival, time to recurrence, time to distant metastases and reduced incidence of contralateral breast cancer compared with tamoxifen – a benefit which increases over time and persists even after treatment ends.2

In ATAC, there were fewer recurrences in women with hormone receptor positive breast cancer treated with anastrozole (n= 2,618) than tamoxifen (n=2,598) at 2, 5 and 9 years post-surgery (91 vs 133; 245 vs 312; 385 vs 488 respectively).1

At a median follow-up of 2 years, compared to tamoxifen, anastrozole:1

- reduces the risk of all recurrences by 32% (HR 0.68 [0.52-0.88])
- reduces the risk of distant metastases by 21% (HR 0.79 [0.58-1.07])
- reduces the incidence of contralateral breast cancer by 78%.

ATAC Trial

The ARIMIDEX, Tamoxifen, Alone or in Combination (ATAC) trial is one of the world’s largest and longest-running clinical studies in postmenopausal women with early breast cancer. ATAC is designed to investigate the comparative efficacy and tolerability of two adjuvant therapies: ARIMIDEX (anastrozole) and tamoxifen.

This analysis of ATAC reinforces the significant superiority of ARIMIDEX over tamoxifen at reducing the risk of breast cancer returning (also known as ‘recurrence’) in postmenopausal women with hormone receptor positive early disease.1 The ATAC data also show that, even approximately four years after treatment completion, the absolute reduction in the risk of disease recurrence continues to increase with ARIMIDEX compared with tamoxifen.2

AstraZeneca

AstraZeneca is a major international healthcare business engaged in the research, development, manufacture and marketing of prescription pharmaceuticals and the supply of healthcare services. It is one of the world’s leading pharmaceutical companies with healthcare sales of $26.47 billion and leading positions in sales of gastrointestinal, cardiovascular, neuroscience, respiratory, oncology and infection products. AstraZeneca is listed in the Dow Jones Sustainability Index (Global) as well as the FTSE4 Good Index. http://www.astrazeneca.com

ARIMIDEX (anastrozole) is a trademark, the property of the AstraZeneca group of companies.

References

1. Howell A, Forbes J, Cuzick J et al. Initial adjuvant therapy with anastrozole – early and late event data from the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial in the hormone-responsive population. St Gallen 2009 Poster

2. Saphner T, Tormey DC, Gray R. Annual hazard rates of recurrence for breast cancer after primary therapy. J Clin Oncol 1996; 14(10): 2738-46

3. ATAC Trialists’ Group. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol 2008; 9: 45-53

4. AstraZeneca IMS data on file

National Breast and Ovarian Cancer Centre (NBOCC) has now released the eagerly anticipated revised version of its Guide for women with early breast cancer. The comprehensive, 200 page resource provides information to support women with early breast cancer* in making decisions about their treatment and care, as well as advice for family and friends. The Guide walks women through every step of their breast cancer journey and is broken down into five key areas: Breast cancer: the facts, Making sense of test results, Treatment, When treatment is over, and Finding support.

“This resource compiles all the information a woman with early breast cancer will need in order to understand her diagnosis, treatment and follow-up care,” said Dr Helen Zorbas, CEO, National Breast and Ovarian Cancer Centre.

Based on NBOCC‘s Clinical practice guidelines for the management of early breast cancer, the consumer guide incorporates the latest evidence in a new, user-friendly, spiral bound format. First released in 2003, the Guide is one of NBOCC’s flagship resources, provided free of charge to women at diagnosis to assist their understanding and decision-making. It has been in consistently high demand with over 110,000 copies disseminated since its first release.

“The Guide provides women with reliable, up-to-date and easy to understand information in a compact booklet that they can take with them as they go through their treatment,” said Dr Zorbas.

To download or order copies of the Guide for women with early breast cancer, visit NBOCC’s website http://www.nbocc.org.au. Orders can also be taken over the phone on 1800 624 973.

* Early breast cancer is cancer that is contained in the breast and may or may not have spread to lymph nodes in the breast or armpit.

National Breast and Ovarian Cancer Centre is funded by the Australian Government and works with consumers, health professionals, cancer organisations, researchers and governments to improve care and cancer control in breast and ovarian cancer.

Bree Stevens
Manager
National Breast and Ovarian Cancer Centre
Level 1, Suite 103, 355 Crown Street SURRY HILLS NSW 2010
http://www.nbocc.org.au

Liz Hardaker, medical director of Cephalon UK. “We are disappointed and surprised that NICE has not taken this opportunity to distinguish between different forms of anthracycline treatment; specifically the use of liposomal-encapsulated doxorubicin.

“Myocet, in combination with cyclophosphamide, is indicated for the first line treatment of metastatic breast cancer in women (SmPC). A number of published clinical trials have shown liposomal-encapsulated doxorubicin to provide improved safety by reducing cardiac toxicity whilst retaining comparable efficacy compared with conventional doxorubicin1,2.

“For patients previously treated with an anthracycline in early breast cancer, Myocet is more effective than doxorubicin with a significantly higher overall objective response rate (ORR) and significantly improved time to treatment failure (TTF).3

“Anthracyclines are a mainstay treatment of metastatic breast cancer but their use is limited by cumulative dose-related cardiotoxicity and myelosuppression, despite long anthracycline-free intervals in many patients. Liposomal-encapsulated doxorubicin was developed to address these toxicity issues1.

“NICE guidelines play an important part in determining appropriate treatment for patients and the failure of NICE to recognise the place of liposomal-encapsulated doxorubicin in its latest guidance may limit access to a treatment that could provide benefit to eligible patients.”

Justin Stebbing, consultant medical oncologist and senior lecturer at Charing Cross Hospital said: “We have approved the use of Myocet in selected patients with breast cancer at Imperial College Healthcare NHS Trust.

“This is based on the data showing efficacy at least as good as other ‘conventional’ anthracyclines, and a lack of cardiac toxicity which is now particularly relevant, as patients with all forms of breast cancer are living longer.”

References:

1 Batist G et al. J Clin Oncol 2001;19(5): 1444-1454.
2 Harris L, Batist G, Belt R et al. Cancer 2002; 94: 26-36
3 Batist G et al. Anti-Cancer Drugs 2006; 17: 587-595.

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Screening for breast cancer risk in all postmenopausal women, using a combination of risk factors and breast density, can identify women at high risk of disease, according to systematic literature reviews and meta-analyses reported in the March 10 online issue of the Journal of the National Cancer Institute. The reviews and meta-analyses also support the use of chemoprevention in women at high risk of disease and the value of positive lifestyle changes in all women irrespective of their breast cancer risk.

Although models have been developed to estimate a postmenopausal woman’s risk of breast cancer, it has not been clear whether the routine use of the models in clinical practice is supported by clinical trial data.

To determine whether regular screening for the risk of breast cancer was justified, Steven Cummings, M.D., of the San Francisco Coordinating Center at the California Pacific Medical Center Research Institute in San Francisco, and colleagues used systematic literature reviews and conducted meta-analyses of clinical trials that examined the predictive accuracy of risk assessment models and breast density measurement to identify women at high risk of disease. They also reviewed prospective studies that examined the impact of lifestyle factors on breast cancer risk, and they conducted a meta-analysis of clinical trials with tamoxifen and raloxifene for primary prevention of breast cancer.

The researchers found that risk assessment models that were based on demographic characteristics and medical history alone had moderate ability to discriminate women’s risk of breast cancer. However, accuracy improved when the models were combined with breast density information. A meta-analysis supported the efficacy of either tamoxifen or raloxifene for primary prevention of breast cancer. Finally, a systematic review and meta-analysis also found that exercise, weight reduction, low-fat diet, and reduced alcohol intake may reduce a woman’s risk of breast cancer.

“In conclusion, evidence from these reviews supports systematic assessment of postmenopausal women for breast cancer risk with risk factors and assessment of breast density. Chemoprevention should be considered for those at high risk; however, cost-benefit analyses are needed to provide specific recommendations about who should be offered chemoprevention,” the authors write. “Several lifestyle changes can be recommended to postmenopausal women, regardless of their estimated risk category.”

Citation:
Prevention of Breast Cancer in Postmenopausal Women: Approaches to Estimating and Reducing Risk.
Cummings et al.
J Natl Cancer Inst 2009;101:384-398.

The Journal of the National Cancer Institute is published by Oxford University Press
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