Breast cancer can be classified into different subtypes based on the presence or absence of certain receptors, such as hormone receptors (estrogen and progesterone) and human epidermal growth factor receptor 2 (HER2). HER2-negative breast cancers do not overexpress the HER2 protein, and as such, treatments targeting HER2, like trastuzumab (Herceptin), are not effective for this subtype. However, there are other targeted therapies available depending on the specific characteristics of the tumor.
For HER2-negative breast cancers that are hormone receptor-positive (i.e., express estrogen and/or progesterone receptors), hormonal therapies can be used as targeted treatments. These include:
Tamoxifen[1]
Tamoxifen is a selective estrogen receptor modulator (SERM) used to treat ER-positive breast cancer. It works by blocking estrogen from binding to estrogen receptors in breast cancer cells. Tamoxifen is often used for 5-10 years after surgery to reduce the risk of recurrence. It has been used for over 30 years and has helped many women with breast cancer.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/020462Orig1s051lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/tamoxifen |
like letrozole, anastrozole, and exemestane
Letrozole is an aromatase inhibitor used to treat postmenopausal women with ER-positive breast cancer. It works by blocking the enzyme aromatase that converts other hormones into estrogen. Letrozole is often used after 5 years of tamoxifen therapy or as the first treatment. It is usually taken daily for 5-10 years.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/021402s015lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/letrozole |
Anastrozole is an aromatase inhibitor used to treat postmenopausal women with ER-positive breast cancer. It works similarly to letrozole by blocking aromatase to lower estrogen levels. Anastrozole is often used after tamoxifen or as the first treatment, and is usually taken daily for 5-10 years.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/022073s010lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/anastrozole |
Exemestane is an aromatase inactivator used to treat postmenopausal women with ER-positive breast cancer. It irreversibly binds to and inactivates aromatase to suppress estrogen production. Exemestane is often used after 2-3 years of tamoxifen, and is usually taken daily for 2-3 years.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022053s010lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/exemestane |
Fulvestrant[5]
Fulvestrant is an estrogen receptor antagonist used in postmenopausal women with ER-positive breast cancer that has progressed. It binds to estrogen receptors and accelerates their degradation. Fulvestrant is often used after aromatase inhibitors, and is given as monthly injections for at least 5 years.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/022053s010lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/exemestane |
Elacestrant is a selective estrogen receptor degrader (SERD) in clinical trials for treating ER-positive breast cancer after resistance to other hormonal therapies. It targets estrogen receptors for degradation to eliminate estrogen signaling. Elacestrant is given as monthly injections and results are promising with good tolerance. If approved, it may provide a new option after hormone resistance.
| Approval Status | https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-elacestrant-er-positive-her2-negative-esr1-mutated-advanced-or-metastatic-breast-cancer |
| Instructions for use:dosing, indications, interactions...etc. | https://reference.medscape.com/drug/orserdu-elacestrant-4000317 |
Palbociclib is a CDK4/6 inhibitor used with letrozole or fulvestrant in ER-positive, HER2-negative breast cancer. It slows cancer cell growth by blocking key enzymes. Palbociclib is given as daily pills for 21 days on and 7 days off, usually for at least 2 years or until disease progression. It can delay disease progression and improve outcomes in advanced breast cancer.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2016/207103s000lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/palbociclib |
Abemaciclib is a CDK4/6 inhibitor used with fulvestrant in HR-positive, HER2-negative breast cancer after progression on hormone therapy. It works similarly to palbociclib to slow cancer growth. Abemaciclib is given twice daily continuously, usually until disease progression. It has been shown to significantly delay disease progression and provide clinical benefit.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209754s000lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/abemaciclib |
Ribociclib is a CDK4/6 inhibitor used with letrozole or fulvestrant in pre/peri-menopausal women with HR-positive, HER2-negative breast cancer. It works similarly to palbociclib and abemaciclib. Ribociclib is given as daily pills for 21 days on and 7 days off, usually for at least 2 years or until disease progression. It can improve outcomes in this population when added to hormone therapy.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209092s000lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/ribociclib |
Alpelisib is a PI3K inhibitor used with fulvestrant in advanced ER-positive, HER2-negative breast cancer with PIK3CA mutations. It blocks the PI3K pathway to inhibit cancer cell growth and survival. Alpelisib is given as daily pills usually until disease progression. In studies, it delayed disease progression and improved outcomes in patients with PIK3CA-mutated breast cancer. It provides a new targeted option for this population.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/212042Orig1s000lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/alpelisib |
For HER2-negative breast cancers that are also hormone receptor-negative (i.e., do not express estrogen or progesterone receptors), the options for targeted therapies are more limited. Some of these therapies are:
These drugs, like olaparib (Lynparza) and talazoparib (Talzenna), are used in patients with BRCA1 or BRCA2 mutations, which are more common in triple-negative breast cancer cases.
Olaparib is a PARP inhibitor used in advanced HER2-negative breast cancer with BRCA mutations. It induces synthetic lethality by inhibiting DNA repair in cancer cells with BRCA mutations. Olaparib is given as daily pills usually until disease progression. It has been shown to significantly delay disease progression and provide clinical benefit with good tolerance in BRCA-mutated breast cancer. Olaparib provides a personalized treatment option for patients with this mutation.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/208192Orig1s013lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/olaparib |
Talazoparib is a potent PARP inhibitor used in advanced HER2-negative breast cancer with BRCA mutations. It has a similar mechanism of action to olaparib. Talazoparib is given as daily pills usually until disease progression. Studies showed it delayed disease progression and prolonged survival with a once daily pill compared to weekly olaparib. Talazoparib provides an alternative PARP inhibitor option.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/209115Orig1s000lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/talazoparib |
Drugs like pembrolizumab (Keytruda) and atezolizumab (Tecentriq) can be used in combination with chemotherapy for some patients with advanced triple-negative breast cancer.
Pembrolizumab is an anti-PD-L1 immunotherapy used in advanced triple-negative breast cancer (TNBC). It blocks the PD-L1/PD-1 interaction to restore anti-tumor immunity. Pembrolizumab is given as intravenous infusion every 3 weeks for up to 2 years or until disease progression or unacceptable toxicity. In studies, it prolonged progression-free and overall survival in patients with PD-L1-positive TNBC. Pembrolizumab is the first immunotherapy approved for TNBC and improves outcomes for this aggressive subtype.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125514Orig1s052lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/pembrolizumab |
Atezolizumab is an anti-PD-L1 immunotherapy used in combination with albumin-bound paclitaxel in advanced TNBC. It works similarly to pembrolizumab. Atezolizumab is given as intravenous infusion before each paclitaxel treatment and then every 2 weeks after completing paclitaxel. In studies, the combination significantly improved outcomes compared to paclitaxel alone in PD-L1-positive TNBC, including prolonged progression-free and overall survival. It provides an alternative immunotherapy option for TNBC.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761034s017lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://www.cancer.gov/about-cancer/treatment/drugs/atezolizumab |
Sacituzumab govitecan is an antibody-drug conjugate used in metastatic TNBC after at least two prior therapies. It targets Trop-2 on breast cancer cells and delivers the chemotherapy irinotecan. Sacituzumab govitecan is given as intravenous infusion on days 1 and 8 of repeated 21-day cycles until disease progression. In studies, it significantly delayed disease progression and improved survival compared to treatment of physician's choice. Sacituzumab govitecan is the first ADC approved for TNBC and provides a new treatment option in this setting.
| Approval Status | https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/761073s000lbl.pdf |
| Instructions for use:dosing, indications, interactions...etc. | https://reference.medscape.com/drug/trodelvy-sacituzumab-govitecan-1000280 |
Other targeted therapies may be available through clinical trials or as part of personalized medicine approaches. It's crucial to consult with a healthcare professional to determine the most suitable treatment options for a specific case of breast cancer.
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