Boston - Nancy U of the Dana-Farber Cancer Institute in the United States. Dr. Lin pointed out at a breast cancer conference sponsored by Harvard Medical School that despite the terrible brain metastasis of breast cancer, recent breakthroughs in some patients suggest that its “terrorist rule†is expected to be broken.
With the improvement of the treatment level, the ranks of women who are still able to survive with advanced breast cancer are growing, and the incidence of brain metastases from breast cancer has also increased. Since the vast majority of existing chemotherapy drugs do not cross the blood-brain barrier, the brain has become an ideal refuge for cancer cells. Current strategies for treating brain metastases cannot effectively improve patient outcomes. However, with the deepening of the understanding of the biological characteristics of primary tumors and the specific sensitivity of tumor subtypes to various treatments, we have been able to create a new era for the treatment of breast cancer brain metastasis, and even prevent its occurrence.
Predominance of tumor subtypes in HER2-positive and triple-negative breast cancer patients is a key consideration in developing prevention strategies. The highest rates of brain metastases in breast cancer are HER2-positive and triple-negative (estrogen receptor-negative, progesterone receptor-negative, HER2-negative) breast cancer patients. There are also significant differences in the prognosis of these subtypes. Although based on historical data, the median survival period after the diagnosis of brain metastases from breast cancer was only 6 months, it has recently been reported that the median survival time of brain metastases in HER2-positive breast cancer patients is 1 to 2 years. The median survival of three-negative breast cancer patients with brain metastases is less than 6 months.
Dr. Lin believes that these differences in survival have important implications for treatment. According to historical data, effective targeted extracranial therapy can prolong the survival of many HER2-positive patients, and more than half of these patients eventually die of central nervous system (CNS) disease progression. For patients with triple-negative breast cancer, brain metastasis and distant metastasis are the main reasons for their short survival time. Therefore, for HER2-positive patients, there is no need to target the treatment of CNS; for patients with triple-negative, there is a need to improve systemic treatment that can affect all metastatic sites.
Although we have gained a deeper understanding of the brain metastasis of breast cancer, the currently available treatment options are very limited. And so far no guidelines have been published for the treatment of breast cancer brain metastases. Surgery, stereotactic radiosurgery, and whole brain radiotherapy are optional local treatments, depending on the number, size and location of the metastases. Conventional breast cancer chemotherapy has also been proven to be an effective first-line treatment.
Dr. Lin and colleagues recently published a review summarizing the considerations for localized and systemic treatment in these patients (Oncology 2012 July 12 [Epub ahead of print]). "First-line treatment usually has a higher response rate than intensified pre-treatment, and it is necessary to identify effective treatments for CNS progression after local or systemic treatment."
Study of lapatinib across the blood-brain barrier In the treatment based on HER2 status, small molecule tyrosine kinase inhibitor (TKI) typerone (Tykerb) continues to receive attention. Due to its small molecular structure, this drug can cross the blood-brain barrier more efficiently than macromolecular drugs (including monoclonal antibodies). This theoretical advantage has already been reflected in clinical trials, resulting in mild benefits. For example, in a single clinical trial of lapatinib, Dr. Lin and colleagues demonstrated that the objective response rate was 2.6%, with clinical benefit in 20% of patients (J. Clin. Oncol. 2008;26:1993-9. ).
In a trial comparing brain metastasis after chemotherapy with lapatinib and capecitabine (Xeloda) or topotecan (Mexin) (J. Neuroncol. 2011;105:613-20), The "objective response rate of CNS was 38%" in the patinib + capecitabine group. Although the study was prematurely terminated due to greater toxicity and lack of efficacy in the topotecan group, the results of the lapatinib plus capecitabine group were encouraging. The key randomized trial of lapatinib has also yielded better results, suggesting that lapatinib may delay the onset of brain metastases in HER2-positive breast cancer patients (Oncologist 2010; 15:924-34).
Mark D, Stanford University. Dr. Pegram pointed out in an accompanying editorial that for newly diagnosed HER2-positive breast cancer patients with brain metastases, immediate treatment with HER2-TKI after neurosurgery and/or radiotherapy may be more effective than waiting for initial treatment. ideal. Still on-going ALTTO [assimilating lapatinib and/or trastuzumab treatment] trials for trastuzumab (Herceptin) alone and trastuzumab plus lapatinib The two adjuvant therapies were compared and the results will allow us to more accurately determine the potential preventive effect of lapatinib on CNS recurrence in early HER2-positive breast cancer.
Several new drugs are being tested in trials. People are also developing more systemic and combination therapies: the new HER2 targeted therapies ranatinib and afatinib. Phase II trials of both drugs are in progress. There are also cytotoxic drugs targeted to brain metastases, including peptide-paclitaxel conjugate GRN1005, glutathione-pegylated liposomal doxorubicin 2B3-101, and third-generation paclitaxel TPI 287; These three drugs are in phase I or phase II trials. In addition, PIK3CA inhibitors, mTOR (rapamycin target protein) inhibitors, PARP (poly ADP ribose polymerase) inhibitors, and VEGF (vascular endothelial growth factor) targeted drugs are also under investigation.
Dr. Lin also emphasized that breast cancer clinical trials often exclude patients with brain metastases, and that in order to make greater progress in preventing and treating breast cancer brain metastases, this situation must be changed.
Dr. Lin disclosed that he has interests in companies such as GlaxoSmithKline, Genentech, Geron, Boehringer Ingelheim, Bayer and Novartis.
With the improvement of the treatment level, the ranks of women who are still able to survive with advanced breast cancer are growing, and the incidence of brain metastases from breast cancer has also increased. Since the vast majority of existing chemotherapy drugs do not cross the blood-brain barrier, the brain has become an ideal refuge for cancer cells. Current strategies for treating brain metastases cannot effectively improve patient outcomes. However, with the deepening of the understanding of the biological characteristics of primary tumors and the specific sensitivity of tumor subtypes to various treatments, we have been able to create a new era for the treatment of breast cancer brain metastasis, and even prevent its occurrence.
Predominance of tumor subtypes in HER2-positive and triple-negative breast cancer patients is a key consideration in developing prevention strategies. The highest rates of brain metastases in breast cancer are HER2-positive and triple-negative (estrogen receptor-negative, progesterone receptor-negative, HER2-negative) breast cancer patients. There are also significant differences in the prognosis of these subtypes. Although based on historical data, the median survival period after the diagnosis of brain metastases from breast cancer was only 6 months, it has recently been reported that the median survival time of brain metastases in HER2-positive breast cancer patients is 1 to 2 years. The median survival of three-negative breast cancer patients with brain metastases is less than 6 months.
Dr. Lin believes that these differences in survival have important implications for treatment. According to historical data, effective targeted extracranial therapy can prolong the survival of many HER2-positive patients, and more than half of these patients eventually die of central nervous system (CNS) disease progression. For patients with triple-negative breast cancer, brain metastasis and distant metastasis are the main reasons for their short survival time. Therefore, for HER2-positive patients, there is no need to target the treatment of CNS; for patients with triple-negative, there is a need to improve systemic treatment that can affect all metastatic sites.
Although we have gained a deeper understanding of the brain metastasis of breast cancer, the currently available treatment options are very limited. And so far no guidelines have been published for the treatment of breast cancer brain metastases. Surgery, stereotactic radiosurgery, and whole brain radiotherapy are optional local treatments, depending on the number, size and location of the metastases. Conventional breast cancer chemotherapy has also been proven to be an effective first-line treatment.
Dr. Lin and colleagues recently published a review summarizing the considerations for localized and systemic treatment in these patients (Oncology 2012 July 12 [Epub ahead of print]). "First-line treatment usually has a higher response rate than intensified pre-treatment, and it is necessary to identify effective treatments for CNS progression after local or systemic treatment."
Study of lapatinib across the blood-brain barrier In the treatment based on HER2 status, small molecule tyrosine kinase inhibitor (TKI) typerone (Tykerb) continues to receive attention. Due to its small molecular structure, this drug can cross the blood-brain barrier more efficiently than macromolecular drugs (including monoclonal antibodies). This theoretical advantage has already been reflected in clinical trials, resulting in mild benefits. For example, in a single clinical trial of lapatinib, Dr. Lin and colleagues demonstrated that the objective response rate was 2.6%, with clinical benefit in 20% of patients (J. Clin. Oncol. 2008;26:1993-9. ).
In a trial comparing brain metastasis after chemotherapy with lapatinib and capecitabine (Xeloda) or topotecan (Mexin) (J. Neuroncol. 2011;105:613-20), The "objective response rate of CNS was 38%" in the patinib + capecitabine group. Although the study was prematurely terminated due to greater toxicity and lack of efficacy in the topotecan group, the results of the lapatinib plus capecitabine group were encouraging. The key randomized trial of lapatinib has also yielded better results, suggesting that lapatinib may delay the onset of brain metastases in HER2-positive breast cancer patients (Oncologist 2010; 15:924-34).
Mark D, Stanford University. Dr. Pegram pointed out in an accompanying editorial that for newly diagnosed HER2-positive breast cancer patients with brain metastases, immediate treatment with HER2-TKI after neurosurgery and/or radiotherapy may be more effective than waiting for initial treatment. ideal. Still on-going ALTTO [assimilating lapatinib and/or trastuzumab treatment] trials for trastuzumab (Herceptin) alone and trastuzumab plus lapatinib The two adjuvant therapies were compared and the results will allow us to more accurately determine the potential preventive effect of lapatinib on CNS recurrence in early HER2-positive breast cancer.
Several new drugs are being tested in trials. People are also developing more systemic and combination therapies: the new HER2 targeted therapies ranatinib and afatinib. Phase II trials of both drugs are in progress. There are also cytotoxic drugs targeted to brain metastases, including peptide-paclitaxel conjugate GRN1005, glutathione-pegylated liposomal doxorubicin 2B3-101, and third-generation paclitaxel TPI 287; These three drugs are in phase I or phase II trials. In addition, PIK3CA inhibitors, mTOR (rapamycin target protein) inhibitors, PARP (poly ADP ribose polymerase) inhibitors, and VEGF (vascular endothelial growth factor) targeted drugs are also under investigation.
Dr. Lin also emphasized that breast cancer clinical trials often exclude patients with brain metastases, and that in order to make greater progress in preventing and treating breast cancer brain metastases, this situation must be changed.
Dr. Lin disclosed that he has interests in companies such as GlaxoSmithKline, Genentech, Geron, Boehringer Ingelheim, Bayer and Novartis.
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