Estrogen Receptor And Progesterone Receptor Positive Breast Cancer
Breast tumors are tested to see if they are estrogen receptor and/or progesterone receptor positive or negative. Hormone receptor tests are both prognostic and predictive. In general, tumors that are ER+ and/or PR+ are slightly slower growing and have a slightly better prognosis than tumors that arent. Hormone receptors also provide information about treatment options. If your tumor is ER+ and/or PR+, then your cancer can be treated with a hormone therapy. For this reason, these tumors are also sometimes referred to as hormone sensitive.
Hormone therapies slow or stop cancers growth by changing the hormonal milieu. For early stage cancer, these treatments include tamoxifen and a class of drugs called aromatase inhibitors or AIs. Currently three aromatase inhibitors are approved for use by the U.S. Food and Drug Administration : anastrozole , letrozole , and exemestane . Studies suggest that all three are equally effective. Women with metastatic breast cancer also have other hormone therapy options, including fulvesrant , megestrol acetate , and tormifene .
Increasing The Dose Of Fulvestrant
The strategy of increasing the dose of fulvestrant has been explored in patients with prior exposure to ET. The CONFIRM study was a multicenter, double-blind, phase III trial that included 736 postmenopausal women with ER+ ABC with progression after tamoxifen or AIs . Patients were randomized to receive 500mg or 250mg of fulvestrant . Results showed that albeit with similar ORR and CBR, the 500mg dose was associated with a small but statistically significant longer PFS . OS was not different at the time of the initial report, but with longer follow up, an unplanned analysis showed a significant 4.1 months difference in favor of the higher dose of fulvestrant. There were no differences in the toxicity profile. The suggested benefit in terms of OS is unique, once very few therapies have demonstrated improvements in survival in patients with HR+ ABC in randomized comparisons. After the publication of these results, fulvestrant at 500mg has become the preferred schedule for this drug in clinical trials . shows selected second-line ET trials.
Should I Enroll In A Clinical Trial
Clinical trials are definitely worth considering, according to the Susan G. Komen organization. They offer the chance to try and possibly benefit from new treatments. The best time to join a trial is before starting treatment or, if your provider is considering changing treatments, before you switch to a new treatment. Ask your doctor if there are any trials that would suit your circumstances. You can also search the clinical trial database at ClinicalTrials.gov or use the Susan G. Komen Metastatic Trial Search, a personalized tool to match you with clinical trials.
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How Can I Tell If My Treatment Is Working
One way youll know is if your pain starts going away, Brufsky says. Your doctor will also monitor your progress every few months with a variety of assessments, which may include a physical exam, blood tests to check for tumor markers, and imaging tests: X-ray, CT scan, PET scan, or bone scan. The results of these tests, combined with the symptoms you report, will help your cancer team understand whether your treatment is helping to control tumor growth, according to Breastcancer.org.
Treatment is typically continued if its working and your side effects are manageable, but if the treatment is no longer working or the side effects are problematic, your doctor may switch you to a different drug. We expect that just about every treatment we choose will work for a period of time and then likely stop working as the cancer develops resistance, Brufsky says. Fortunately, we have many treatments that are effective with HR-positive/HER-2-negative metastatic breast cancer.
What Are The Side Effects Of Hormone Therapy
The side effects of hormone therapy depend largely on the specific drug or the type of treatment . The benefits and harms of taking hormone therapy should be carefully weighed for each person. A common switching strategy used for adjuvant therapy, in which patients take tamoxifen for 2 or 3 years, followed by an aromatase inhibitor for 2 or 3 years, may yield the best balance of benefits and harms of these two types of hormone therapy .
Hot flashes, night sweats, and vaginal dryness are common side effects of all hormone therapies. Hormone therapy also may disrupt the menstrual cycle in premenopausal women.
Less common but serious side effects of hormone therapy drugs are listed below.
Tamoxifen
- Breathing problems, including painful breathing, shortness of breath, and cough
- Loss of appetite
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Clinicopathologic Characteristics Of Single Hormone Receptor
The median follow-up duration for the 6,980 patients included in this analysis was 45 months . In this study, 4,651 cases were double HR+ tumors, 1,758 were double HR- tumors, and 571 cases were single hormone-receptor positive tumors, of which 90 cases were ER-PR+ tumors and 481 were ER + PR- tumors. The clinicopathological characteristics of the four subtypes are summarized in Table . Overall, ER+/PR- tumors were found more frequently in postmenopausal women than other subtypes . Compared with ER + PR+ tumor, ER + PR- tumors were not significantly different in staging , but ER+PR- tumors exhibited higher nuclear grade , higher Ki-67 level , and higher EGFR and HER2 expression . However, compared with ER-PR- tumors, ER + PR- tumors showed lower stage , lower NG , lower Ki-67 level , lower p53 expression and lower EGFR expression , but there was no difference in HER2 overexpression .
Table 1 Clinicopathologic characteristics of patients with ER + PR+, ER + PR-, ER-PR+ and ER-PR- tumors
ER-PR+ tumors had higher NG , higher Ki-67 level , and higher expression of p53 and EGFR than ER + PR+ tumors. However, compared with ER-PR- tumors, there was no difference in stage or NG . Also, there was no difference in expression of Ki-67 , p53 , EGFR or HER2 .
Is Stomach Cancer Hereditary
Stomach cancer is the second leading cause of cancer related deaths worldwide and in India, the fourth in the list of the most common cancers. As per the US National Institutes of Health close to ten percent of stomach cancer cases have a familial origin. Having a first degree relative such as father, mother, brother or sister with stomach cancer increases the risk of developing stomach cancer.
While gene mutations have been linked to stomach cancer in some people, the exact genetic factors are not fully understood. Scientists believe a combination of environmental and genetic factors could be responsible for familial stomach cancer.
Some of the inherited conditions that increase stomach cancer risk include:
Hereditary diffuse gastric cancer :
This is an inherited, rare condition that increases risk of stomach cancer caused by a mutation in a gene known as CDH1.
Diffuse gastric cancer also known as or linitis plastica orsignet ring cell gastric cancer affects almost the entire stomach rather than any one specific area in the stomach. According to the NIH, diffuse gastric cancers account for 20 percent of stomach cancers and HDGC is responsible for a small amount of these cancers. Women diagnosed with HDGC are at an increased risk of developing breast cancer.
Diagnosis of HDGC is made if any one criteria listed below are met apart from recommending CDH1 genetic testing:
Lynch syndrome:
Li-Fraumeni syndrome:
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Combination Of Endocrine And Targeted Therapies In The First
The combination of targeted therapy and ET is an evolving field. Preclinical evidence suggests that targeting mechanisms of ET resistance, such as the PIK3CA/AKT/mTOR pathway, the cell cycle machinery and the cross talk between HR and growth factor receptor signaling, among others, might increase or restore endocrine sensitivity. Despite stimulating data from preclinical studies with a variety of agents and targets, only recently have randomized clinical trials demonstrated significant benefit with these approaches. Anti-human epidermal growth factor receptor type 2 agents, mammalian target of rapamycin and cyclin-dependent kinase 4/6 inhibitors are already incorporated in the clinical care of patients with HR+ ABC both in first- and second-line settings. Trials with PIK3CA inhibitors and anti-vascular endothelial growth factor agents have also been presented. reviews selected positive trials and reviews selected ongoing trials evaluating the strategy of combining targeted agents to avoid or reverse resistance to ET.
Combination Of Endocrine Therapies
As the available anti-endocrine drugs have different mechanisms of action, combination of agents is a logical approach to improve the effectiveness of ET. Conflicting results have been reported from the comparison of the combination of fulvestrant with anastrozole versus anastrozole as single agent. The FACT trial reported no clinical advantage with the combination , while the SWOG S0226 trial reported advantages in PFS and OS favoring the combination in 694 ABC patients . Subgroup analysis of this trial suggested that the benefits were largely restricted to women who had not received adjuvant tamoxifen and differences in the population included probably explain the conflicting results in the two studies. Furthermore, results of the second-line SoFEA trial showed that combining fulvestrant to anastrozole is not more effective that fulvestrant alone or exemestane alone in HR+ ABC that has progressed during therapy with a nonsteroidal AI. A subgroup analysis suggested those patients with tumors with both ER and PR positivity, favoring a more endocrine-sensitive phenotype, may obtain greater benefit . Based on these data, it could be hypothesized that patients with ET-naïve ABC and those with highly endocrine-sensitive tumors could derive the largest benefit from combination ET. However, in our opinion, we should wait for further evidence before considering the combination of AIs and fulvestrant in routine clinical practice . First-line ET trials are summarized in .
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Proteins For Targeted Cancer Drugs
Testing cancer cells for particular proteins can help to show whether targeted drug treatments might work for your breast cancer.
Targeted cancer drugs are treatments that change the way cells work and help the body to control the growth of cancer.
Some breast cancers have large amounts of a protein called HER2 receptor . They are called HER2 positive breast cancers. About 15 out of every 100 women with early breast cancer have HER2 positive cancer.
Targeted cancer drugs such as trastuzumab can work well for this type of breast cancer. These drugs attach to the HER2 protein and stop the cells growing and dividing.
Hormone Therapy After Surgery For Breast Cancer
After surgery, hormone therapy can be given to reduce the risk of the cancer coming back. Taking an AI, either alone or after tamoxifen, has been shown to work better than taking just tamoxifen for 5 years.
These hormone therapy schedules are known to be helpful for women who are post-menopausal when diagnosed:
- Tamoxifen for 2 to 3 years, followed by an AI for 2 to 3 years
- Tamoxifen for 2 to 3 years, followed by an AI for 5 years
- Tamoxifen for 4½ to 6 years, followed by an AI for 5 years
- Tamoxifen for 5 to 10 years
- An AI for 5 to 10 years
- An AI for 2 to 3 years, followed by tamoxifen for 2 to 3 years
- For women who are unable to take an AI, tamoxifen for 5 to 10 years is an option
For most post-menopausal women whose cancers are hormone receptor-positive, most doctors recommend taking an AI at some point during adjuvant therapy. Standard treatment is to take these drugs for about 5 years, or to take in sequence with tamoxifen for 5 to 10 years. For women at a higher risk of recurrence, hormone treatment for longer than 5 years may be recommended. Tamoxifen is an option for some women who cannot take an AI. Taking tamoxifen for 10 years is considered more effective than taking it for 5 years, but you and your doctor will decide the best schedule of treatment for you.
These therapy schedules are known to be helpful forwomen who are pre-menopausal when diagnosed:
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Risks For Breast Cancer
A risk factor is something that increases the risk of developing cancer. It could be a behaviour, substance or condition. Most cancers are the result of many risk factors. But sometimes breast cancer develops in women who dont have any of the risk factors described below.
Most breast cancers occur in women. The main reason women develop breast cancer is because their breast cells are exposed to the female hormones estrogen and progesterone. These hormones, especially estrogen, are linked with breast cancer and encourage the growth of some breast cancers.
Breast cancer is more common in high-income, developed countries such as Canada, the United States and some European countries. The risk of developing breast cancer increases with age. Breast cancer mostly occurs in women between 50 and 69 years of age.
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Endocrine Breast Cancer Therapy Interferes With Er And Pr Hormone Uptake
Endocrine therapy frequently involves treatment with either tamoxifen or an aromatase inhibitor. These agents interfere with the hormone receptors in the breast cancer cells, making it very difficult for the malignant cells to grow and spread. As a result, hormone-receptor positive tumors generally have a better outlook than hormone-receptor negative breast tumors.
In other words, the hormone receptor positive breast cancer status can help predict how the cancer will behave. In that sense, the hormone receptor status of a breast tumor is more of a predictive indicator rather than a prognostic indicator.
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Will I Get Breast Cancer If I Take Hrt
Wondering if hormone therapy causes breast cancer? Studies are all over the place in terms of whether or not HRT increases your risk. Even though the WHI found that estrogen-only hormone replacement therapy reduced breast cancer risk, a number of other studies have found that both types of HRT did in fact increase breast cancer risk. Theres no clear answer at this point in time as to whether or not HRT increases the risk of breast cancer.
Side note: Since we are talking about cancer and the risk of getting it, I do want to mention that the risk of getting cancer does increase with age naturally. According to the National Cancer Institute , the median patient age at the time of a cancer diagnosis is 66. Advancing age is the most important risk factor for cancer overall,the NCI website says.
From night sweats to achy joints, menopausal symptoms can be debilitating for some people. If this is you, then by all means talk to your doctor about treatment options. Ask your healthcare provider how you can treat your symptoms while reducing your risk of breast cancer. Also, be sure to discuss the pros and cons of the different types of HRT and doses.
American Society Of Clinical Oncology Guidelines
In 2014, the American Society of Clinical Oncology published a Clinical Practice Guideline to address systemic therapy for patients with advanced HER2+ breast cancer.43 These guidelines are formulated by a multidisciplinary group of experts using a review of phase III randomized controlled trials and their clinical experience. The guidelines that are relevant to first-line treatment are reviewed here.
HER2-targeted therapy combinations should be recommended for first-line treatment, except for highly selected patients with ER- and/or PR-positive breast cancers who may receive endocrine therapy alone . This recommendation is based on trials, including the pivotal trial by Slamon and colleagues,2 which showed that HER2-targeted therapy in combination with chemotherapy in the first-line setting led to improvements in response rates, PFS, TTP, and OS compared with chemotherapy alone. In the endocrine therapy trials,39,40 the addition of HER2-targeted therapy improved RR and PFS but not OS.
The combination of trastuzumab, pertuzumab, and taxane should be recommended for first-line treatment, unless the patient has a contraindication to taxane treatment . This recommendation is based on the CLEOPATRA trial,18,19 which showed an improvement in PFS and OS. The panel felt that paclitaxel could be used in place of docetaxel. The data for other chemotherapy agents were more limited, and the panel felt that these should generally be avoided until more data are available.
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Hormone Receptor Status And Hormone Therapy
Hormone receptor-positive breast cancers can be treated with hormone therapy drugs. These include tamoxifen and the aromatase inhibitors, anastrozole , letrozole and exemestane . Ovarian suppression, with surgery or drug therapies, is also a hormone therapy.
Hormone receptor-negative breast cancers are not treated with hormone therapies because they dont have hormone receptors.
Learn about hormone therapy for the treatment of metastatic breast cancers.
How Her2 Affects Staging
Your HER2 status helps determine the pathology of your specific breast cancer. Your HER2 status can also help determine how aggressive the cancer is. Your doctor will use this information to evaluate your treatment options.
As of 2018, the breast cancer staging system that the American Joint Committee on Cancer uses now incorporates HER2 status.
Staging is complex and must take various other factors into account, such as:
- the size of the tumors
- whether the cancer has spread to nearby lymph nodes
- whether the cancer has spread beyond the breast
- whether the cancer cells look abnormal
For example, these two cancers are both classified as stage 1B:
| HER2-negative |
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What Do The Hormone Receptor Test Results Mean
Test results will give you your hormone receptor status. It will say a tumor ishormone receptor-positive if at least 1% of the cells tested have estrogen and/or progesterone receptors. Otherwise, the test will say the tumor is hormone receptor-negative.
Hormone receptor-positive breast cancer cells have either estrogen or progesterone receptors or both. These breast cancers can be treated with hormone therapy drugs that lower estrogen levels or block estrogen receptors. Hormone receptor-positive cancers tend to grow more slowly than those that are hormone receptor-negative. Women with hormone receptor-positive cancers tend to have a better outlook in the short-term, but these cancers can sometimes come back many years after treatment.
Hormone receptor-negative breast cancers have no estrogen or progesterone receptors. Treatment with hormone therapy drugs is not helpful for these cancers. These cancers tend to grow faster than hormone receptor-positive cancers. If they come back after treatment, its often in the first few years. Hormone receptor-negative cancers are more common in women who have not yet gone through menopause.
Triple-positive cancers are ER-positive, PR-positive, and HER2-positive. These cancers can be treated with hormone drugs as well as drugs that target HER2.