Annual Screening with Breast Ultrasound or MRI Could Benefit Some Women

Results of a large-scale clinical trial presented presented at the 95th Scientific Assembly and Annual Meeting of the Radiological Society of North America (RSNA) provide the first strong evidence of the benefit of annual screening ultrasound for women with dense breasts who are at elevated risk for breast cancer. In addition, the study confirmed that MRI is highly sensitive in depicting early breast cancer.

"We found that annual screening with ultrasound in addition to mammography significantly improves the detection of early breast cancer," said lead researcher Wendie A. Berg, M.D., Ph.D., breast imaging specialist at American Radiology Services, Johns Hopkins — Green Spring Station in Lutherville, Md., "and that significantly more early breast cancer can be found when MRI is performed, even after combined screening with both ultrasound and mammography. However, both ultrasound and MRI increase the risk of false-positive findings."

Women who are at high risk for breast cancer need to begin screening at a younger age, because they often develop cancer earlier than women at average risk. However, women below age 50 are more likely to have dense breast tissue, which can limit the effectiveness of mammography as a screening tool.

Multicenter trials have shown that MRI enables radiologists to accurately identify tumors missed by mammography and ultrasound. The American Cancer Society recommends that some groups of women with a high risk of developing breast cancer should be screened with MRI in addition to their yearly mammogram beginning at age 30. However, MRI is not for everyone.

"Because MRI is a very expensive test and requires intravenous contrast, it is something we only recommend for screening the approximately 2% of women who are known or likely carriers of BRCA1 or BRCA2 gene mutations or have other unusual circumstances that put them at very high risk for breast cancer," Dr. Berg said.

"There are another 10 to 15% of women who are at some increased risk because of personal history of breast cancer, family history of breast cancer and/or dense breast tissue," she added. "For many of these women, MRI is not currently justified, but annual ultrasound would be appropriate in addition to mammography."

Fig 1. This breast MRI showing focus of enhancement in left breast, negative on mammography and screening ultrasound. Pathology proven infiltrating ductal carcinoma

The researchers studied 612 women, mean age 55 years, at elevated risk of breast cancer enrolled at 14 sites in the American College of Radiology Imaging Network (ACRIN) 6666 trial funded by the Avon Foundation and the National Cancer Institute. Women underwent baseline screening mammography and ultrasound with follow-up exams at 12 and 24 months and then a single, contrast-enhanced MRI at 24 months.

Sixteen women were diagnosed with breast cancer. Twelve of the cancers were invasive, and four were ductal carcinoma in situ (DCIS). Over the course of the study, 50 to 56 percent of cancers were shown on mammography. Adding ultrasound allowed detection of 70 to 94% of cancers. Adding MRI allowed for detection of additional cancers at their earliest stage.

Fig 2. Ultrasound showing 9-mm benign mass (arrows) in upper inner quadrant

The study also found that supplemental screening with ultrasound or MRI significantly increased the risk of false-positive findings, leading to unnecessary biopsies in some women.

"It is important that women are advised of the increased potential of undergoing an unnecessary biopsy as a result of screening with ultrasound or MRI," Dr. Berg said, "but we hope this study motivates women and their doctors to learn more about their risk factors and to consider supplemental screening in addition to mammography where indicated."

Also see Abstracts:
Supplemental Yield and Performance Characteristics of Screening MRI after Combined Ultrasound and Mammography: ACRIN* 6666 *American College of Radiology Imaging Network.

Sorafenib (Nexavar®) Significantly Improves the Length of Time Before Breast Cancer Worsens: Results From First, Large Randomized Trial

Approximately 30 studies evaluating the use of sorafenib (Nexavar®, Bayer Healthcare Pharmaceuticals/Onyx Pharmaceuticals)tablets across tumor types – as a single agent or in combination with other therapies – were presented at Europe’s largest cancer congress, the joint 15th European CanCer Organisation (ECCO) and 34th European Society for Medical Oncology (ESMO) Multidisciplinary Congress, September 20 – 24 in Berlin.

“The presentations at the ECCO/ESMO conference continue to build on our large body of data in unresectable liver cancer and advanced kidney cancer where sorafenib has a proven track record,” said Dimitris Voliotis, Vice President, Global Clinical Development Oncology. “Additionally, we are very enthusiastic about the presented Phase 2 studies evaluating the safety and efficacy of sorafenbib in other tumor types, including breast and thyroid cancers.”

One of the first of a series of trials to investigate the use of sorafenib – a targeted anti-cancer drug – for the treatment of advanced breast cancer has found that if it is combined with the chemotherapy drug, capecitabine (Xeloda®, Roche, Basel, Switzerland), it makes a significant difference to the time women live without their disease worsening.

Principal investigator of the study, Professor José Baselga told his audience: “This is the first, large, randomized study that demonstrates significant clinical activity of sorafenib in breast cancer when given in combination with chemotherapy. Our results showed that patients who received sorafenib plus capecitabine had a 74% percent improvement in the time they lived without their disease worsening compared to those who received the chemotherapy alone. This is a very positive study and the magnitude of the benefit is such that it suggests that this agent will be an important addition to our therapeutic armory in breast cancer.”

Sorafenib is a potent multi-kinase inhibitor, which works by interfering with the growth of cancer cells and slowing the growth of new blood vessels within the tumor. Until now, it has only been used in the treatment of kidney and liver cancer.

Prof Baselga, who is head of the oncology department at Vall d’Hebron University Hospital (Barcelona, Spain), president of ESMO (European Society for Medical Oncology) and a member of the ECCO (European CanCer Organization) executive committee, and his colleagues in Spain, France and Brazil enrolled 229 patients with locally advanced or metastatic breast cancer in the double-blind, randomized phase II clinical trial between June 2007 and December 2008. They randomized the patients to receive capecitabine (1000 mg/m2 pill taken twice daily for 14 of every 21 days) and a placebo (114 women), or capecitabine and sorafenib (400 mg pill taken twice daily continuously) for 115 women.

The very first results from the trial only became available in time for the ECCO 15 – ESMO 34 congress, and they show that the average progression free survival (the time that elapses without the cancer getting worse) was 6.4 months for women on capecitabine and sorafenib compared to 4.1 months for women taking the placebo. It is too early for data on overall survival to be available. The only death that occurred was in the placebo arm of the trial, attributed to the effect of capecitabine. The number of patients discontinuing treatment due to adverse side-effects was nine (8%) in the placebo arm and 15 (13.4%) in the sorafenib arm of the trial.

Prof Baselga said: “The regimen was tolerable and the side-effects were mostly manageable. No new or unexpected side effects were observed with this combination. The fact that this treatment could be taken orally may represent a unique and convenient treatment option for patients with breast cancer.

“This trial is an example of good academia and industry partnership. It was designed and conducted by the Spanish breast cooperative group SOLTI with the participation also of Brazilian and French groups. The trial was fully supported by Onyx and Bayer. Based on the encouraging data from this trial so far, Onyx and Bayer are evaluating various strategies for sorafenib in breast cancer.

“This trial is the first of a series of randomized phase II studies with sorafenib that are currently underway in breast cancer. Based on our results, we believe that the drug shows considerable promise for the treatment of the disease.”

For more information:

• Jose Baselga, M.D., Vall d'Hebron University Hospital in Barcelona, Spain. A double-blind, randomized phase 2b study evaluating the efficacy and safety of sorafenib (SOR) compared to placebo (PL) when administered in combination with capecitabine (CAP) in patients (pts) with locally advanced (adv) or metastatic (met) breast cancer (BC). Late-breaking abstract 3LBA, Presidential Session III, Wednesday, September 23, 1:30 p.m., Hall 1

Other trial results:

Hepatocellular Carcinoma

• Jean-Luc Raoul, M.D., Centre Eugène Marquis, Rennes, France. Effect of Macroscopic Vascular Invasion (MVI), Extrahepatic Spread (EHS), and ECOG Performance Status (ECOG PS) on Outcome in Patients with Advanced Hepatocellular Carcinoma (HCC) Treated with Sorafenib: Analysis of Two Phase 3, Randomized Double-Blind Trials. Abstract 6621, Poster 309, Wednesday, September 23, 2009, 2 p.m. – 5 p.m., Hall 14.1
• Josep Llovet, M.D., Barcelona Clinic Liver Cancer (BCLC) Group, Liver Unit, CIBERehd, IDIBAPS, Hospital Clinic Barcelona, Barcelona, Spain. Efficacy and Safety of Sorafenib in Patients with Advanced Hepatocellular Carcinoma (HCC): Collective Results from the Phase III Sorafenib HCC Assessment Randomized Protocol (SHARP) and Asia-Pacific (AP) Trials. Abstract 6519, Poster 13, Tuesday, September 22, 2009, 8 a.m. – 11 a.m., Poster Discussion, 11:15 a.m. – 12:15 p.m., Central Lobby (Outside Hall 3)

Renal Cell Carcinoma

• Joachim Beck, M.D., Johannes-Gutenberg-Universität III. Medizinische Klinik, Mainz, Germany. Final Analysis of a Large Open-label, Noncomparative, Phase 3 Study of Sorafenib in European Patients with Advanced RCC (EU-ARCCS). Abstract 7137, Poster 150, Monday, September 21, 2009, 2 p.m. – 5 p.m., Hall 14.1
• Hideyuki Akaza, M.D., Institute of Clinical Medicine, University of Tsukuba, Ibaraki, Japan. Efficacy and Safety of Long-term Use of Sorafenib: Final Report of a Phase II Trial of Sorafenib in Japanese Patients with Unresectable/Metastatic Renal Cell Carcinoma. Abstract 7147, Poster 160, Monday, September 21, 2009, 2 p.m. – 5 p.m., Hall 14.1
• Ronald M. Bukowski, M.D., Cleveland Clinic Taussig Cancer Center, Cleveland, OH. Efficacy and Safety of Sorafenib in Patients with Advanced Clear-Cell Renal-Cell Carcinoma (RCC) with Bone Metastases: Results from the Phase III TARGET Study Abstract 7130, Poster 143, Monday, September 21, 2009, 2 p.m. – 5 p.m., Hall 14.1
• Dirk Jäger, M.D., National Center for Tumor Diseases, University of Heidelberg, Heidelberg, Germany. PREDICT (Patient characteristics in REnal cell carcinoma and Daily practICe Treatment with Nexavar) Global Non-interventional Study: First interim results. Abstract 7128, Poster 141, Monday, September 21, 2009, 2 p.m. – 5 p.m., Hall 14.1

Thyroid Cancer

• Marcia Brose, M.D., Ph.D. Department of Medicine, Division of Hematology/Oncology and Department of Otorhinolaryngology: Head and Neck Surgery, Abrahamson Cancer Center of the University of Pennsylvania, Philadelphia, PA, U.S.A. Completion of a Phase II study of sorafenib for advanced thyroid cancer. Late-breaking poster 51LBA, Poster 276, Tuesday, September 22, 11 a.m. – 1:00 p.m. Hall 14.1

Highlights of Prescribing Information:

• Sorafenib (Nexavar ®)
• Capecitabine (Xeloda®)

Also read these Pubmed Abstracts:

• Higgins MJ, Forastiere A, Marur S. New directions in the systemic treatment of metastatic thyroid cancer. Oncology (Williston Park). 2009 Aug;23(9):768-75.
• Bianchi G, Loibl S, Zamagni C, Salvagni S, Raab G, et al. Phase II multicenter, uncontrolled trial of sorafenib in patients with metastatic breast cancer. Anticancer Drugs. 2009 Aug;20(7):616-24.
• Hill KL Jr, Lipson AC, Sheehan JM. Brain magnetic resonance imaging changes after sorafenib and sunitinib chemotherapy in patients with advanced renal cell and breast carcinoma. J Neurosurg. 2009 Sep;111(3):497-503.
  Pytel D, Sliwinski T, Poplawski T, Ferriola D, Majsterek I. Tyrosine kinase blockers: new hope for successful cancer therapy Anticancer Agents Med Chem. 2009 Jan;9(1):66-76. Review.
• Schraml C, Schwenzer NF, Martirosian P, Bitzer M, et al. Diffusion-weighted MRI of advanced hepatocellular carcinoma during sorafenib treatment: initial results. AJR Am J Roentgenol. 2009 Oct;193(4):W301-7.
• Sugawara M, Geffner DL, Martinez D, Hershman JM. Novel treatment of medullary thyroid cancer. Curr Opin Endocrinol Diabetes Obes. 2009 Oct;16(5):367-72.

New Mammography Technology Effective in Detecting Breast Cancer

Positron emission mammography or PEM, a new technique for imaging the breast, is not affected by either breast density or a woman’s hormonal status, two factors that limit the effectiveness of standard mammography and MRI at detecting cancer, according to a study presented during the 94th Scientific Assembly and Annual Meeting (November 30 – December 5, 2008) of the Radiological Society of North America (RSNA) on Tuesday.

“The ability of positron emission mammography or PEM to detect cancer does not appear to be adversely affected by breast density, hormone replacement therapy or menopausal status,” explained the lead researcher Kathy Schilling, M.D., director of breast imaging and intervention at the Center for Breast Care at Boca Raton Community Hospital in Florida. “The sensitivity of PEM is equal to or better than breast MRI, and PEM has fewer false-positive results.”

The ability of x-ray mammography, a standard screening tool for breast cancer, to detect lesions is reduced when performed on dense breasts, where tissue is less fatty and more glandular. Breast MRI is effective at detecting cancer in dense breasts and is increasingly being used to screen women at high risk for breast cancer. However, MRI has a high incidence of false-positive test results that indicate cancer is present when it is not. Researchers believe these false positives are due in part to hormonal changes that occur during a woman’s menstrual cycle.

“Unless the MRI is performed on day seven through 14 of a woman’s cycle, reading MRI images is extremely difficult,” Dr. Schilling said. “This is a significant problem with breast MRI.” Because hormones do not have the same effect on PEM results, Dr. Schilling believes the imaging technique could play a significant role both in preoperatively evaluating breast cancer patients and in screening high-risk patients.

In the study, 208 patients with breast cancer underwent PEM, an application of high-resolution breast positron emission tomography (PET) in which a small amount of radioactive material is injected into the body to measure metabolic activity and determine the presence of disease. The researchers used a PET unit specially developed for the breast and small body parts to perform the PEM exam.

Of 189 malignant lesions imaged, PEM detected 176 for an overall sensitivity rate of 93 percent. Fifteen percent were ductal carcinoma in situ (DCIS), a noninvasive cancer confined to the ducts of the breast; 85 percent were invasive cancer.

PEM successfully detected cancer in 100 percent of fatty breasts, 93 percent of dense breasts, 85 percent of extremely dense breasts, 93 percent of women both with and without a history of hormone replacement therapy, 90 percent of pre-menopausal women and 94 percent of post-menopausal women.

According to Dr. Schilling, PEM is well tolerated by patients, who sit upright during the exam and are not alone or closely confined as they would be during an MRI exam. While breast MRI exams produce more than 2,000 images to be interpreted, PEM produces just 48 images that can be correlated with a woman’s mammogram.

“PEM is easier to use, easier to interpret and easier on the patients than MRI,” Dr. Shilling said. “It is also ideal for those patients whose MRI is difficult to interpret due to hormonal influences, women with implants, patients with metal in their bodies, or patients who suffer from claustrophobia. It is exciting that we now have a functional imaging approach with high sensitivity that complements our current anatomic imaging modalities,” she added.

Positron Emission Mammography at a Glance

• Positron emission mammography (PEM) is an effective tool for detecting breast cancer.
• Dense breast tissue and hormonal status can hinder other breast imaging techniques.
• PEM shows high sensitivity and is not limited by these factors.
• PEM, also known as high-resolution breast PET, has fewer false-positive results than breast MRI.
  

Click here to read the abstract (Effect of Breast Density, Menopausal Status, and Hormone Use in High Resolution Positron Emission Mammography).