Lani
10-31-2012, 10:53 PM
As with most things, the story turns out not to be as simple as originally presented...
Moderately Expressed Protein is Adverse Prognostic Factor for Breast Cancer
[PRWeb]
Prognosis for breast cancer after surgery is adverse even when a key protein is expressed moderately and without an amplification of its associated oncogene, a new study published in The Oncologist has found, suggesting that protein-inhibitor treatment would be beneficial for a larger group of patients than previously thought.
The study, led by Dr. Filippo Montemurro, MD, from the Unit of Investigative Clinical Oncology and Division of Medical Oncology at the Institute for Cancer Research and Treatment in Torino, Italy, examined how varying levels of overexpression of HER-2 (human epidermal growth factor receptor) might predict breast cancer outcomes and found that more moderate expressions of HER-2 serve as adverse prognostic factors for patients with operable breast cancer.
"These findings suggest rethinking HER-2 status with respect to prediction of trastuzumab-related benefit in patients with early breast cancer and also, in our opinion, prognostic terms," Dr. Montemurro said.
Biologically, the expression of HER-2 - a type of protein found in more aggressive types of breast cancer - falls on a continuous spectrum, but current tests like HercepTest™ use algorithms and categories to match treatments to the patients who would benefit most from them. Breast cancer treatments such as adjuvant trastuzumab specifically target HER-2 to inhibit its growth.
While HER-2 testing in patients with operable breast cancer is aimed at identifying candidates for treatment, Dr. Montemurro's study focused on whether the expression of variable levels of HER-2 also influenced prognosis. Using HercepTest™ and fluorescence in situ hybridization (FISH) when needed, researchers determined the HER-2 status of 1,150 women undergoing surgery for early breast cancer at the Institute. Dr. Montemurro and his colleagues studied the impact of HER-2 status on disease-free survival (DFS) time and other pathological features.
They found that patients whose tumors had lower levels of overexpression, and no amplification, had a distinct adverse prognosis. In particular, patients with HercepTest scores of +2, and with no associated amplification of the HER-2/neu oncogene, have adverse prognosis that is slightly better than patients with the most overexpression (+3 and HER-2/neu amplification) during the first 4 to 5 years after surgery, but that worsens in later years.
"Dr. Montemurro's observations are provocative and point out how complex the HER-2 field is," said Dr. Gabriel N. Hortobágyi, MD, Senior Editor of The Oncologist. "Added to the observations by Soon Paik about potential benefit from trastuzumab in patients with 1+ and 2+ HER-2 overexpression, these data emphasize the need for additional, careful research to fully understand the implications of the full spectrum of HER-2 overexpression and amplification."
Dr. Montemurro and his colleagues recommended that further testing be done to build on their findings and to confirm whether patients with more moderate HER-2 levels would, in fact, benefit from treatments similar to those received by patients with higher levels of HER-2 and HER-2/neu amplification.
ABSTRACT: Moderate Immunohistochemical Expression of HER-2 (2+) Without HER-2 Gene Amplification Is a Negative Prognostic Factor in Early Breast Cancer
[The Oncologist]
Background: Human epidermal growth factor receptor (HER)-2 testing in patients with operable breast cancer is aimed at identifying candidates for adjuvant anti-HER-2 treatment. However, commonly defined "HER-2-" tumors express variable levels of the HER-2 protein, which can influence prognosis. We compared the clinical outcomes of operable breast cancer patients stratified according to a common HER-2 testing algorithm.
Methods: We studied 1,150 women (median age, 58 years; range, 22-94 years) undergoing surgery for early breast cancer at our institution. HER-2 status was determined using the HercepTest™ (Dako, Glostrup, Denmark) and, when needed, by fluorescence in situ hybridization (FISH). Patients receiving adjuvant trastuzumab were excluded. The impact of HER-2 status on the disease-free survival (DFS) time was studied using multivariate Cox proportional regression analysis.
Results: Four hundred-fifty seven (40%), 454 (39%), 116 (10%), and 123 (11%) patients were considered HER-2 0+, HER-2 1+, HER-2 2+/HER-2- by FISH, and HER-2+ (3+ or HER-2+ by FISH), respectively. Compared with a HER-2 0 or 1+ status, a HER-2 2+/HER-2- by FISH status was associated with a worse DFS outcome on multivariate analysis. Compared with a HER-2+ status, a HER-2 2+/HER-2- status showed a time-dependent effect on the DFS probability, with an initial advantage that worsened every year by a factor of 1.649.
Conclusion: A HER-2 2+/HER-2- status is an adverse prognostic factor in patients with operable breast cancer. Because of suggestions from randomized trials that the benefits of adjuvant trastuzumab may not be limited to patients with HER-2+ tumors, patients with a HER-2 2+/HER-2- status are ideal candidates for studies testing this hypothesis.
Moderately Expressed Protein is Adverse Prognostic Factor for Breast Cancer
[PRWeb]
Prognosis for breast cancer after surgery is adverse even when a key protein is expressed moderately and without an amplification of its associated oncogene, a new study published in The Oncologist has found, suggesting that protein-inhibitor treatment would be beneficial for a larger group of patients than previously thought.
The study, led by Dr. Filippo Montemurro, MD, from the Unit of Investigative Clinical Oncology and Division of Medical Oncology at the Institute for Cancer Research and Treatment in Torino, Italy, examined how varying levels of overexpression of HER-2 (human epidermal growth factor receptor) might predict breast cancer outcomes and found that more moderate expressions of HER-2 serve as adverse prognostic factors for patients with operable breast cancer.
"These findings suggest rethinking HER-2 status with respect to prediction of trastuzumab-related benefit in patients with early breast cancer and also, in our opinion, prognostic terms," Dr. Montemurro said.
Biologically, the expression of HER-2 - a type of protein found in more aggressive types of breast cancer - falls on a continuous spectrum, but current tests like HercepTest™ use algorithms and categories to match treatments to the patients who would benefit most from them. Breast cancer treatments such as adjuvant trastuzumab specifically target HER-2 to inhibit its growth.
While HER-2 testing in patients with operable breast cancer is aimed at identifying candidates for treatment, Dr. Montemurro's study focused on whether the expression of variable levels of HER-2 also influenced prognosis. Using HercepTest™ and fluorescence in situ hybridization (FISH) when needed, researchers determined the HER-2 status of 1,150 women undergoing surgery for early breast cancer at the Institute. Dr. Montemurro and his colleagues studied the impact of HER-2 status on disease-free survival (DFS) time and other pathological features.
They found that patients whose tumors had lower levels of overexpression, and no amplification, had a distinct adverse prognosis. In particular, patients with HercepTest scores of +2, and with no associated amplification of the HER-2/neu oncogene, have adverse prognosis that is slightly better than patients with the most overexpression (+3 and HER-2/neu amplification) during the first 4 to 5 years after surgery, but that worsens in later years.
"Dr. Montemurro's observations are provocative and point out how complex the HER-2 field is," said Dr. Gabriel N. Hortobágyi, MD, Senior Editor of The Oncologist. "Added to the observations by Soon Paik about potential benefit from trastuzumab in patients with 1+ and 2+ HER-2 overexpression, these data emphasize the need for additional, careful research to fully understand the implications of the full spectrum of HER-2 overexpression and amplification."
Dr. Montemurro and his colleagues recommended that further testing be done to build on their findings and to confirm whether patients with more moderate HER-2 levels would, in fact, benefit from treatments similar to those received by patients with higher levels of HER-2 and HER-2/neu amplification.
ABSTRACT: Moderate Immunohistochemical Expression of HER-2 (2+) Without HER-2 Gene Amplification Is a Negative Prognostic Factor in Early Breast Cancer
[The Oncologist]
Background: Human epidermal growth factor receptor (HER)-2 testing in patients with operable breast cancer is aimed at identifying candidates for adjuvant anti-HER-2 treatment. However, commonly defined "HER-2-" tumors express variable levels of the HER-2 protein, which can influence prognosis. We compared the clinical outcomes of operable breast cancer patients stratified according to a common HER-2 testing algorithm.
Methods: We studied 1,150 women (median age, 58 years; range, 22-94 years) undergoing surgery for early breast cancer at our institution. HER-2 status was determined using the HercepTest™ (Dako, Glostrup, Denmark) and, when needed, by fluorescence in situ hybridization (FISH). Patients receiving adjuvant trastuzumab were excluded. The impact of HER-2 status on the disease-free survival (DFS) time was studied using multivariate Cox proportional regression analysis.
Results: Four hundred-fifty seven (40%), 454 (39%), 116 (10%), and 123 (11%) patients were considered HER-2 0+, HER-2 1+, HER-2 2+/HER-2- by FISH, and HER-2+ (3+ or HER-2+ by FISH), respectively. Compared with a HER-2 0 or 1+ status, a HER-2 2+/HER-2- by FISH status was associated with a worse DFS outcome on multivariate analysis. Compared with a HER-2+ status, a HER-2 2+/HER-2- status showed a time-dependent effect on the DFS probability, with an initial advantage that worsened every year by a factor of 1.649.
Conclusion: A HER-2 2+/HER-2- status is an adverse prognostic factor in patients with operable breast cancer. Because of suggestions from randomized trials that the benefits of adjuvant trastuzumab may not be limited to patients with HER-2+ tumors, patients with a HER-2 2+/HER-2- status are ideal candidates for studies testing this hypothesis.