Her2 neu overexpression at level 3. HER2 tests and breast cancer
Breast cancer is the leading cause of cancer death among women in the world. The HER-2 test is shown to every woman with an established diagnosis of breast cancer, its importance cannot be overestimated - it is the main fulcrum in the choice of further targeted therapy.
What is HER2?
To understand the nature of HER2, one must learn about receptors and growth factors.- Receptors- These are certain proteins that are on the membrane of cells or inside them. Other proteins or chemicals found in the body can attach to these receptors to effect a change within the cell (for example, cause it to repair or reproduce).
- growth factors are chemical compounds that attach to receptors and stimulate cell growth.
What is HER status?
The HER2 receptor is a protein molecule and is therefore also called the HER2 protein or HER2 protein. It shows the content of the HER2 gene and HER2 protein in tumor cells. HER2 status of breast cancer can be negative or positive.Why is HER-2 analysis needed?
Determination of HER2 status is extremely important, because based on the result of the study, doctors in Israel make a decision on the tactics of treating the patient. Depending on the presence of biological tumor markers (estrogen and / or progesterone receptors, HER2 receptors), hormone-positive, HER2-positive and triple-negative breast cancer are isolated. There are currently drugs in Israel that target the HER2 receptor.What does a positive HER2 status mean?
In HER2-positive breast cancer, there is an excess of HER2 receptors on the surface of the tumor cells. This phenomenon is called “positive HER2 status. When overexpressed, HER2 receptors on the membrane disrupt the normal cell cycle and force cells to divide uncontrollably. A similar phenomenon was noticed by researchers in a quarter of patients with breast cancer. If the tumor is HER2 positive, the patient is indicated for targeted anti-HER2 therapy.What does HER negative status mean?
Some cancer cells breasts may have many more HER2 receptors than others. In this case, the tumor is defined as HER2 positive. It is estimated that one in five women with breast cancer is HER2 positive.What is positive breast cancer?
Breast cancer with an increased content (amplification) of the HER 2 gene or accelerated production (overexpression) of the HER2 receptor is called HER 2-positive. He is considered especially aggressive. It is diagnosed in about 25% of breast cancer cases. Tumors of this type progress very quickly, but the glands can be treated with special drugs Herceptin and Lapatinib, as well as the new drug Beyodyme.It is important to note that over time, approximately 30% of HER2-positive breast cancers become HER2-negative.
What is Negative Breast Cancer?
Breast cancer with a normal HER2 gene and HER2 receptor is called HER 2 negative. This type of cancer is determined in approximately 75% of patients with breast cancer. In HER2-negative tumors, Herceptin therapy is not indicated due to its low efficacy.How is HER-2 breast cancer status determined in Israel?
To determine the HER2 status of breast cancer, namely to identify advanced level HER 2 gene in tumor cells, special tests are applied from tumor tissue taken during a biopsy. Tests can be carried out simultaneously with the initial stage of surgical intervention.The two main methods used for HER2 testing are immunohistochemistry and fluorescent in situ hybridization (FISH):
1. Immunohistochemical study(IHC)
2. FISH test(fluorescent hybridization) FISH is the most accurate test for detecting elevated levels of the HER 2 gene in breast tumor cells.
3. SPOT-LIGHT HER 2 CISH test
4. INFORM HER 2 DUAL ISH test
The latest US-approved Inform HER2 Dual ISH test has been used in Israel since 2010.
The results of the Inform HER2 Dual ISH test are similar to the tests above and are also categorized into positive and negative breast cancer.
HER2 and hormone therapy
Hormone therapy can slow or stop the growth of breast cancer cells. This happens by changing the level of certain female hormones that are naturally produced by the body, or preventing the absorption of hormones by cancer cells.Hormone therapy is effective when a woman's cancer cells have estrogen and/or progesterone receptors. They are defined as estrogen or progesterone positive. There are many various kinds hormone therapy and they are only slightly different from each other.
HER2 test
Tests may be done to determine if a woman has HER2-positive breast cancer. Tests may be performed at the same time as the first stage of surgery. Cancer tissue samples from previous biopsies or surgery may be used.Who needs a HER2 status test?
Modern treatment of breast cancer is unthinkable without determining the HER2 status. All women diagnosed with breast cancer should be tested to determine the HER2 status in tumor cells, since this status is extremely important both for prognosis and for the selection of adequate treatment.Determination of HER2 status allows you to purposefully prescribe drugs, Lapatanib, or in cases where they will be effective, i.e. only in HER2 positive breast cancer.
Can HER2 status change over time?
Yes maybe. Studies show that in 30 percent of cases, HER2-positive breast cancer eventually transforms into HER2-negative.Israel currently has effective drugs that target the HER2 receptor. In the group of patients with IHC 3+, IHC 2+/ISH-positive tumors, targeted HER2 therapy is used.
New in breast cancer treatment
Currently, several types of chemotherapy drugs, targeted therapy drugs and hormone therapy are used to treat breast cancer - Tamoxifen, Herceptin, Bayodyme and others. The optimal treatment is selected by Israeli doctors after a thorough study of the histological findings and medical history.Predicting and assessing the need for chemotherapy before it starts
A unique diagnostic technique for patients with early stage breast cancer
When diagnosed in the early stages of estrogen receptor-containing breast cancer, the diagnostic will help you and your doctor choose the most suitable chemotherapy drugs for you in addition to your treatment plan. In addition, this test can help predict the risk of future recurrences of the disease. And most importantly, it will help you avoid unnecessary, unnecessary treatment and get the necessary targeted therapy, not calculated on the statistics of your disease, but selected for you individually.Call us for free
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To purchase the medicine you need, please fill out the contact form. We will contact you within an hour, please prepare your prescription for the necessary drug, we will tell you the exact cost with shipping from Israel. Malignant tumors of the breast are among the most common diseases with lethal outcome among the female population throughout the world. They are leading among cancers, and account for about 11% of the total number of diagnosed oncological neoplasms.
Fortunately, the current level of development of medicine has reduced the mortality rate of women suffering from breast cancer, due to the discovery of modern drugs for chemotherapy, and improved screening with the possibility of earlier diagnosis.
Before making an accurate diagnosis and starting the necessary therapy for breast cancer, you need to find out the biological portrait of the tumor. This description should include:
- Tumor stage;
- The presence of metastases;
- Proliferative activity index ki-67;
- HER2 status.
HER 2 is a gene, (Human Epidermal Growth Factor Receptor 2) - the human receptor for epidermal growth factor 2. It is a transmembrane protein that has a huge role in the processes of movement of growth signals at the cellular level. HER2 belongs to the family of HER proteins, which consist of 4 types of growth factor receptors: HER1, HER2, HER3, HER4.
In normal physiology, HER2 promotes signaling that regulates division and life cycle cells, but its overexpression can cause malignant mutation. The relationship between HER2 overexpression and carcinogenesis has been well studied in the case of breast cancer in women (approximately 30% of women with breast cancer have a HER2 positive type), and this type of oncological process is one of the main markers of gastrointestinal cancer (about 15-20% of cases of stomach damage). or esophagus are HER2 positive).
Today's cancer diagnosis necessarily includes the determination of HER2 status, based on the diagnostic results obtained, doctors make a prognosis for further treatment and patient survival. The hallmark of HER2-positive breast cancer is its increased aggressiveness (it grows and spreads much faster than HER2-negative type). But despite this, HER2-positive cancer shows excellent success rates for therapy with specific drugs Herceptin and Lapatinib, which will not help in the diagnosis of HER2-negative breast cancer.
Diagnostics
The best method for studying HER2 cancer type is considered to be a pathoanatomical study, which is carried out in two ways (immunohistochemistry and in situ hybridization). These techniques help to see the most complete picture of the pathological process, calculate the morphological characteristics and interpret the quantitative expression of HER2.
Immunohistochemistry- is a method of microscopic examination using a bright field, in which a parallel determination of HER2 status is carried out, and tissue morphology is assessed. IHC is a fairly simple method, it is carried out quickly and does not require large financial costs (which is used by many pathoanatomical laboratories).
But relying only on the results of this method is unreasonable, since the criteria for assessing IHC are largely subjective and semi-quantitative, which in some cases leads to incorrect results.
Material that has been assessed as IHC-2 positive should be retested using the in situ hybridization method to obtain a more reliable result.
In situ hybridization (FISH)) is a microscopic examination technique, but already in a dark field, for which DNA probes are used that are associated with a fluorescent label to quantify the level of amplification of the HER2 gene. The technique involves binding the HER2 probe to the HER2 gene locus on chromosome 17, while the CEP17 probe binds to the centromeric region of chromosome 17.
The resulting research response is estimated as the proportion of the number of copies of the HER2 gene to the number of copies of chromosome 17. A sample is considered FISH positive if the HER2:CEP17 ratio is greater than or equal to 2.0.
In most cases, in situ is used to confirm indeterminate IHC results, but it can be used as an initial and main method.
Those patients who used the hybridization method as the primary diagnostic method, and their samples are assessed as positive, are immediately referred for anti-HER2 therapy. If IHC was used as the primary method, in situ hybridization should be performed on all IHC 2+ results to confirm HER2 status and quantify HER2 gene amplification. Targeted tumor treatment is effective for female patients with HER2 overexpression (ie HER2 positive cancer type).
Conclusions were drawn about patients with IHC3+ results who have a positive HER2 status, but IHC 0/1+ was negative. In this case, IHC2+ samples are considered indeterminate and are subject to retesting by in situ hybridization. IHC 2+/ISH sample is positive, considered HER2 positive.
If the doctor has doubts about the IHC3+ result, he decides to re-determine the HER2 status, but using a different method.
Treatment
Increased activity of the HER2 receptor is observed in approximately 1/3 of all female patients diagnosed with breast cancer, which is associated with negative prognoses about the course of the process and the reaction of the neoplasm to chemotherapy and hormone therapy. Overexpression of these receptors makes cancer more aggressive. This makes it possible to predict the progression of the process, and provides an opportunity to determine targets for targeted action on malignant cells that contain this receptor.
The HER2 gene affects the production of the HER2 protein, belongs to proto-oncogenes, that is, despite the fact that the protein normally has a regulatory function, any deviation in the HER2 genes can become a predisposing factor for the onset of cancer, which is why the status indicator is important in the diagnosis of cancer HER2.
About 30% of breast cancer patients have an increased amount of the HER2 protein. If we compare such patients with women who have HER2 negative type, we can find out that the first group lends itself to a more complex course of the oncological process and rapid development, and chemotherapy-type treatments can only aggravate their condition.
Features of HER2+ cancer:
- There is a high percentage that it recurs after treatment.
- Practice shows that HER2+ cancer responds poorly to treatment with anticancer drugs, which are the standard treatment for breast cancer. Also, the negative effects of the use of standard chemotherapy methods for the treatment of this type of cancer have been proven, they are expressed in the form of an increase in protein production, and an increase in the rate of tumor growth.
Starting early targeted therapy with Herceptin helps to prevent early progression of education by blocking HER2 receptors. Modern specialists in the field of oncology use advanced therapy methods that show excellent results due to the direct effect on the altered target cells. Conclusions were drawn regarding the use of the drug Herceptin (patients who started treatment with this drug in the early stages have a 50% lower prognosis for relapse than those patients who were not treated with this drug).
During the use of Herceptin in parallel with chemotherapy, half of the patients observe the complete disappearance of the tumor. If small particles remain, surgeons can easily remove them. Survival after such a course of treatment increases significantly, and metastases are not detected for many years.
Herceptin is prescribed to patients with a HER2 positive tumor type, which can be determined using the methods described above, they should be carried out in the laboratories of oncological dispensaries. The drug is prescribed for IHC3+, in the case of 1+ or 2+, it is necessary to use another method - FISH.
Treatment with Herceptin is appropriate only for HER-2 positive patients.
Forecast
The presence of HER2-positive cancer belongs to the group with an unfavorable prognosis, and this form is less amenable to chemotherapy and hormonal therapy. But the use of a targeted method of treatment and its combination with traditional ones, which is possible only with this type, has significantly increased the chances of survival and the prognosis for successful treatment of this disease in the last 10 years.
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For citation: Ganshina I.P. Hyperexpression of HER2/NEU - new opportunities in the treatment of breast cancer // BC. 2005. No. 13. S. 869
Progress in molecular biology and biotechnology has opened up new possibilities in the treatment of patients with malignant neoplasms. As a result of many years of research, some of the mechanisms for controlling cell division and cell death have been established. It has been shown that proteins involved in carcinogenesis provide additional information about the behavior of the tumor, including its growth rate, the ability to invade and metastasize, and resistance to chemotherapy drugs. Blocking the activity of certain receptors and proteins leads to a decrease in the tumor and prolongation of the life of patients. There are new possibilities for predicting the course of the disease and choosing a reasonable, individualized therapy.
HER2 and its role
in a normal cell
The HER2 gene, also known as c-erbB-2 or HER2/neu, was first discovered in rat neuroblastoma (hence the designation neu). The gene product is the HER2/neu transmembrane glycoprotein, which is a member of the epidermal growth factor receptor (EGFR) family.
All members (HER1, HER2, HER3, HER4) of the EGFR family play an important role in the normal development and differentiation of cells. Stimulation of this receptor leads to the launch of transcriptional mechanisms, which accelerates cell proliferation and growth.
In humans, the HER2/neu receptor is detected in normal tissues, but its overexpression is characteristic only of tumor cells. The significance of HER2 overexpression has been most studied in breast cancer.
Significance of HER2 overexpression
in breast cancer
HER2/neu overexpression is detected in 25–30% of breast cancer cases, and in 90–95% of cases, HER2/neu overexpression is a direct result of c–erbB–2 gene amplification.
Preclinical and clinical studies have shown that amplification and/or overexpression of HER2 is of key importance in oncotransformation and tumorigenesis of breast cancer.
Hyperexpression of HER2/neu in a tumor cell correlates with a number of unfavorable prognostic factors, namely: tumor size, high grade of malignancy, and a decrease in estrogen and progesterone receptors in the tumor.
A large number of studies have shown that HER2/neu overexpression is an independent prognostic factor for N+ and N– breast cancer.
It is important for the clinician to know that as a result of HER2/neu overexpression, the effectiveness of chemotherapy and endocrine therapy with tamoxifen decreases and, most importantly, recurrence-free and overall survival decreases.
Thus, the relationship between overexpression and/or amplification of HER2/neu and poor clinical prognosis gives grounds to consider HER2 as an important link in the pathogenesis of breast cancer, as well as a new and important target for therapy. As a result, a drug with a fundamentally new mechanism of antitumor action was synthesized - trastuzumab.
Herceptin is a recombinant humanized anti-p185HER2 monoclonal antibody that binds highly selectively to the extracellular domain of the HER2/neu receptor. It has been shown that this suppresses the proliferation of human tumor cells that overexpress HER2/neu. In addition to direct antiproliferative action, Herceptin is able to induce a pronounced reaction of antibody-dependent cellular cytotoxicity, specifically directed at tumor cells overexpressing HER2. Herceptin has also shown anti-angiogenic activity.
The effectiveness of Herceptin depends on the correct determination of the indications for the appointment. Today, Herceptin is recommended only for patients with HER2 overexpression (IHC 3+, or IHC 2+ and FISH-positive).
There are currently two modes of use for Herceptin:
1. Weekly intravenous administration at a dose of 2 mg / kg, 30-minute infusion (first dose 4 mg / kg, 90-minute infusion) - the regimen is recommended for practical use.
2. Introduction once every 3 weeks intravenously at a dose of 6 mg / kg, 90-minute infusion (first dose 8 mg / kg, 90-minute infusion) - can be used as an alternative to the weekly regimen for long-term treatment of patients.
Important: Herceptin must only be administered in physiological sodium chloride solution!
Herceptin is generally well tolerated by patients. During the first infusion, 40% of patients developed infusion reactions, consisting of chills and / or fever. Rarely, nausea, vomiting, dizziness, and asthenia are added to these symptoms. Symptoms of an infusion reaction are well treated with corticosteroids and antihistamines.
After the first injection, acute infusion reactions (shortness of breath, anaphylaxis) may occur with a frequency of 3 per 1000, extremely rarely they can be life-threatening. Therapeutic measures give a quick effect. In the future, treatment with Herceptin can be continued with premedication, which ensures the safety of treatment. Given the possibility of acute infusion reactions, patients should be observed for at least 6 hours after the start of Herceptin infusion (i.e. 4.5 hours after the end of the infusion).
Treatment of metastatic
breast cancer
overexpressing HER2
Herceptin is now firmly established in the treatment of HER2 overexpressing breast cancer and is the only drug that, in combination with chemotherapy, increases the time to progression compared to the group of patients who did not receive Herceptin.
Herceptin can be used for the treatment of metastatic HER2 positive breast cancer in combination with taxanes, vinorelbine, cisplatin-containing regimens, capecitabine as the first line of treatment, as well as in monotherapy in the II-III line.
Herceptin on its own
application
As a result of initial clinical research it was proved that Herceptin has independent antitumor activity (Table 1).
In a study by Cobleigh et al. the overall response rate was 15% (4% CR + 12% PR). This response rate metric produces great impression, especially considering that patients belong to the group of poor prognosis, and also previously received more than one line of chemotherapy. The median duration of remission was 9.1 months with Herceptin treatment and was significantly longer than after previous chemotherapy - 5.2 months. The median overall survival was 13 months. In cases of a positive response to Herceptin, the median time to the development of resistance was 11 months, while in the previous chemotherapy regimens in these same patients it was 5.4 months. This study also compared the rate of clinical remission, taking into account the degree of overexpression of HER2/neu. It was found that the higher the degree of HER2 overexpression (+++), the more effective Herceptin therapy.
Thus, the independent antitumor activity of Herceptin was established in advanced breast cancer with HER2+.
Herceptin in combination with cytotoxic agents for the treatment of HER2+ metastatic breast cancer
In preclinical studies, an increase in the antitumor activity of some cytostatics in combination with Herceptin (in particular, doxorubicin, platinum derivatives, taxanes, vinorelbine) was found. Numerous clinical studies have indicated significant success and some problems with the combination of Herceptin with chemotherapy.
A randomized, multicenter, phase III study (HO648g) compared the efficacy of combination chemotherapy with the inclusion of Herceptin and chemotherapy alone in patients with metastatic breast cancer in the first line of treatment.
Patients (HER23+ or HER22+) not receiving adjuvant anthracyclines were randomized to doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 with or without Herceptin. Patients receiving anthracycline-containing regimens in the postoperative period were randomized to receive paclitaxel with or without Herceptin. The results of the study are shown in table 2.
The results of this study show that the addition of Herceptin to paclitaxel is associated with an increase in overall response rate (49% vs. 17%) and a longer time to progression (7.1 vs. 3 months) (Figure 1).
The combination of Herceptin with doxorubicin and cyclophosphamide not only did not increase the frequency of the therapeutic effect, but also marked the problem of cardiotoxicity when using this combination. The incidence of heart failure in the Herceptin + paclitaxel group was 8.8–11%, compared with 1–4% in patients in the paclitaxel monotherapy group. The frequency of clinically manifested heart failure in the Herceptin + paclitaxel group did not significantly differ from that in paclitaxel monotherapy (p = 0.24). Heart failure was detected in 26–28% of patients treated with Herceptin in combination with AC, which significantly exceeded those in the AC group (6–9%). Multivariate analysis showed that independent risk factors for heart failure included: prior anthracycline therapy, concomitant use of Herceptin and doxorubicin, elderly age and traditional NYHA cardiac risk factors.
However, it should be noted that after discontinuation of treatment, in most cases, heart failure is reversible, but treatment with Herceptin cannot be continued.
Given the increased risk of cardiotoxicity, the combination of Herceptin + doxorubicin is not recommended.
Subsequently, a series of non-randomized studies was conducted confirming the effectiveness of the combination of paclitaxel with Herceptin (Table 3). The overall effect in these studies ranged from 36 to 81%.
No less effective was the combination of Herceptin and docetaxel in the first line of chemotherapy for metastatic breast cancer.
In the treatment of 280 patients, the efficiency ranged from 44 to 83% (Table 4).
Comparative study M77001 investigated the efficacy of the combination docetaxel ± Herceptin in the first line treatment of HER2 overexpressing metastatic breast cancer. The study included 188 patients with metastatic breast cancer with HER2 overexpression, approximately 70% of patients received adjuvant chemotherapy (64% of patients in the Herceptin + docetaxel group and 55% in the docetaxel group received anthracyclines). Ninety-four patients received 6 courses of docetaxel 100 mg/m2 monotherapy, and 94 patients received 6 courses of docetaxel 100 mg/m2 in combination with Herceptin on a weekly basis until disease progression. The results of the study are presented in table 5.
The results of the randomized study M77001 confirmed the high efficacy of the combination of docetaxel with Herceptin (overall response 61%) compared with docetaxel alone (overall response 34%) as a first-line treatment for metastatic breast cancer (MBC). The median time to progression in the first group was 10.6 months. compared with 5.7 months. in the second group. The median overall survival in the Herceptin + docetaxel group was 30.5 months, and in the docetaxel monotherapy group it was 22.1 months.
Based on the presented data, the combination of Herceptin + taxanes (paclitaxel, docetaxel) is recommended as the first line of treatment for metastatic breast cancer with HER2 overexpression.
Herceptin in combination
with vinorelbine
Vinorelbine is one of the active drugs for the treatment of metastatic breast cancer. It has a favorable toxic profile, which allows effective treatment without compromising the quality of life of patients.
Preclinical data demonstrate synergy between vinorelbine and Herceptin.
Burstein et al. published the results of a phase II study of 40 women with HER2+ metastatic breast cancer. Vinorelbine was prescribed at a dose of 25 mg/m2, weekly, Herceptin - in a standard weekly regimen as I-III line of treatment. The overall effectiveness was 75% and 84% for groups of patients treated as the first line. Moreover, the time to progression in the I line therapy group was more than 34 weeks, while in the II–III line therapy group it was 16 weeks.
Similar data confirming the high efficiency of the combination of vinorelbine (30 mg/m2 weekly) and Herceptin (4 mg/kg day 1, then 2 mg/kg weekly) in the first line of MBC treatment are shown in the work of Jahanzeb M. et al. In the treatment of 40 patients, the overall effect rate was 78%, with 82% for HER23+ and 58% for HER22+.
ASCO 2005 reported the results of a study of the combination of Herceptin + vinorelbine in the first line of treatment for metastatic breast cancer with HER2 overexpression. The study involved 69 patients who received vinorelbine 30 mg/m2 weekly and Herceptin weekly. The overall effectiveness of the regimen was 61%, the average duration of the effect was 12 months, and the 1-year disease-free survival rate was 39%.
Thus, the combination of Herceptin and vinorelbine in patients with advanced breast cancer is highly effective, safe and requires further study both in the first and subsequent lines of treatment.
Herceptin in combination
with platinum derivatives and taxanes
Cisplatin and carboplatin are being studied in combination with Herceptin and taxanes based on preclinical evidence of synergy between platinum derivatives, Herceptin and taxanes.
In a study by Slamon D.J. et al. an increase in grade III–IV cardiac toxicity (NYHA) has been shown when Herceptin is co-administered with doxorubicin. Given these data, combinations of Herceptin with platinum derivatives and taxanes are promising for further study of their effectiveness as adjuvant therapy.
The Breast Cancer Research Group (BCIRG) conducted 2 phase II multicentre studies. The first study evaluated the efficacy of docetaxel 75 mg/m2, cisplatin 75 mg/m2 in combination with Herceptin on a weekly basis. In the second study, docetaxel 75 mg/m2, Carboplatin AUC 6 and Herceptin on a weekly basis. In each study, 62 patients received treatment. Grade III–IV cardiac toxicity in these studies was minimal, at 3.2% in the first study and 1.6% in the second study. The overall efficacy in the cisplatin-containing regimen was 79%, the median time to progression was 9.9 months (in the general group), in the FISH+ group it was 12.7 months. For carboplatin-containing regimen - the overall effectiveness of 56%, the median time to progression of 12 months. in the general group and 17 months. – in the FISH+ group.
The results of a phase III randomized trial also proved the high efficacy of the combination of Herceptin + paclitaxel + carboplatin in the first line of treatment for metastatic breast cancer.
196 patients were randomized into 2 groups: group 1 received paclitaxel 175 mg/m2, 6 cycles + Herceptin on a weekly basis, group 2 - paclitaxel 175 mg/m2, carboplatin AUC 6 + Herceptin on a weekly basis. The results of the study are presented in table 6.
Thus, the addition of carboplatin to the combination of Herceptin + paclitaxel increases both the immediate efficacy of treatment (57% versus 37% in the subgroup of patients with a HER23+ tumor) and the median time to progression (14 months versus 7.1 months in the subgroup of patients with a HER23+ tumor). ).
Based on the data on the efficacy of Herceptin in combination with carboplatin and docetaxel, the Breast Cancer Research Group (BCIRG) began studying this combination in adjuvant regimens compared with anthracycline-containing regimens followed by the use of docetaxel (4 courses of AC + 4 courses of docetaxel) in patients with early stages HER2+ breast cancer.
Herceptin in combination
with capecitabine
Monotherapy with capecitabine in metastatic breast cancer has shown high efficacy and a favorable toxic profile. In combination with docetaxel, capecitabine increases survival compared to docetaxel alone. Preclinical data indicate that capecitabine has at least an additive effect in combination with Herceptin.
In a study by Bangemann et al. capecitabine 2500 mg/m2, days 1–14 + Herceptin weekly as a third-line treatment for HER2+ metastatic breast cancer. The effectiveness of the regimen was 60%, the median time to progression was 28 weeks.
Phase II results indicate that the combination of Herceptin with capecitabine is effective and well tolerated. These data led to a study (MO16419) comparing the efficacy of Herceptin + docetaxel with or without capecitabine. Another study (MO17038) plans to compare the efficacy of capecitabine ± Herceptin in the second line of treatment in patients with advanced breast cancer with HER2+ after the combination of Herceptin + docetaxel in the first line.
Neoadjuvant therapy
breast cancer
overexpressing HER2
The high activity of the combination of paclitaxel and docetaxel with Herceptin in metastatic breast cancer has become the basis for its study in neoadjuvant regimens. Paclitaxel (175 mg/m2 every 3 weeks) in combination with weekly Herceptin was used in neoadjuvant chemotherapy in patients with stage II-III breast cancer. The number of courses conducted was 4. Among 40 operated patients, complete disappearance of the tumor was achieved according to the morphological study in 18% of cases, complete + partial clinical remission - in 75% of cases.
In another study, locally advanced and edematous infiltrative breast cancer was treated with a combination of Herceptin + docetaxel + cisplatin. Of the 16 operated patients, the clinical complete effect was recorded in 100%, and the complete morphological effect in 25%.
Harris et al. studied the efficacy of a combination of Herceptin (weekly) with vinorelbine (25 mg/m2 - weekly) in stage II-III breast cancer with HER2 overexpression. 39 included patients received treatment for 12 weeks. The frequency of objective clinical effect was 92%, complete morphological remission - 21%.
Endocrine therapy for breast cancer with HER2 overexpression
Analysis of the receptor status in cases of breast cancer with HER2 overexpression showed that 45 - 49% is combined with positive estrogen receptors (Table 7).
To date, there is ample evidence from preclinical and clinical studies proving that HER2 overexpression is associated with resistance to hormone therapy with tamoxifen. There is evidence that tumors overexpressing HER2 and ER+ are more sensitive to antiaromatase therapy than to tamoxifen.
A study comparing the efficacy of aromatase inhibitors letrozole and tamoxifen in the neoadjuvant regimen in patients with HER2/neu+ER+ overexpression was performed. The remission rate was 88% for letrozole and 21% for patients treated with tamoxifen. This may mean that letrozole is able to overcome drug resistance in HER2 positive patients.
Similar data confirming the effectiveness of antiaromatase drugs were obtained in the IMPACT study, in which patients with resectable breast cancer received preoperative endocrine therapy with tamoxifen, anastrozole, or a combination of anastrozole and tamoxifen. The frequency of objective effect in the group of patients with HER2 positive status receiving anastrozole was 58% compared with 22% in the tamoxifen group.
A phase II study evaluating the efficacy of the combination of Herceptin with letrozole included 26 patients with tamoxifen-resistant breast cancer with HER2+/ER+ and/or PR+. Patients received letrozole daily + Herceptin on a weekly or 3-week basis until disease progression. Of the 22 cases evaluated, 9% had a full effect, and 18% had a partial effect. The median time to progression was 31 weeks (15–47 weeks).
The results of this study indicate the effectiveness of the combination of Herceptin with letrozole in a group of patients resistant to standard endocrine therapy. However, this study includes a small number of patients as well as patients with HER22+. Further study of the effectiveness of the combination of Herceptin and aromatase inhibitors in large randomized trials is required.
A randomized trial MO16772, which is planned to include 300 patients, has been launched to evaluate the effectiveness of the combination of letrozole ± Herceptin in the first line of treatment for metastatic breast cancer with HER2+/ER+.
Preclinical data indicate that the combination of Herceptin with tamoxifen may be more effective than the use of drugs in monotherapy.
A phase III randomized trial is currently planned to compare the efficacy of the Herceptin ± Tamoxifen combination as a 2nd line treatment for HER2+/ER+ metastatic breast cancer after 1st line chemotherapy or endocrine therapy.
Adjuvant therapy for HER2 overexpressing breast cancer
A series of studies are currently underway on the adjuvant use of Herceptin after completion of standard chemotherapy regimens (NSAPB B-31, BCIRG 006, PACS 004, HERA) .
Interim results of the HERA study were reported at ASCO 2005. The study included 5090 patients with early stages of breast cancer who completed adjuvant therapy.
Herceptin was prescribed once every 3 weeks (8–6 mg/kg) depending on randomization: group 1 - Herceptin therapy for 1 year, group 2 - Herceptin therapy for 2 years, group 3 - no Herceptin treatment .
As a result of the analysis, according to the data of 12 months. observations found that the use of Herceptin significantly (by 50%) reduces the risk of developing distant metastases compared with the control group (p Conclusion
Hyperexpression of HER2/neu in breast cancer predicts a high risk of recurrence of the disease, its aggressive course, and reduced survival.
HER2/neu+ predicts reduced efficacy of chemotherapy and endocrine therapy with tamoxifen in breast cancer.
Determination of HER2 status should become a routine research method.
The indication for the appointment of Herceptin is the overexpression of HER2 - IHC 3+ or IHC 2+ and FISH +.
The combination of Herceptin and taxanes in HER2 overexpressing MBC significantly improves efficacy and overall survival.
The combination of Herceptin with taxanes is recommended as the first line of treatment for metastatic breast cancer.
Intermediate 12 months the results of the HERA study showed a significant (50%) reduction in the risk of developing distant metastases compared with the control group (p
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7 Hotaling TE, Reitz B The humanized anti-HER2 antobody rhuMAB Her2 mediates antibody depends on cell-mediated cytotoxicity via FcgRIII. Proceedings of the American Association of Cancer Research 37 471.
8 Izumi, Y., Xu, L., di Tomaso, E., Fukumura, D., Jain, R. K. Tumor biology: Herceptin acts as an anti-angiogenic cocktail. Nature - 2002. - Vol. 416. - P. 279 - 280.
9 Carbonell Castellon X., et al. Efficacy and safety of 3-weekly Herceptin monotherapy in women with HER-positive metastatic breast cancer. Proc ASCO 2002; 19.
10 Cobleigh MA, Vogel CL et al. Multinational study of the efficacy and safety of humanized anti–HER2 monoclonal antibody in women who have HER2–overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999; 17:2639–48.
11 Vogel CL, Cobleigh MA et al. Efficacy and safety of trastuzumab as a single agent in first–line treatment of HER2–overexpressing metastatic breast cancer. J Clin Oncol 2002; 20:719–26.
12 Slamon DJ et al. Use of chemotherapy plus a monoclonal antibody against HER2 for metatstatic breast cancer that overexpresses HER2. N Engl J Med 2001; 344:783–92.
13 Leyland-Jones B, Gelmon K, Ayoub J-P, et al. Pharmacokinetics, safety, and efficacy of trastuzumab was administered every three weeks in combination with paclitaxel. J Clin Oncol 2003;21:3965–71.
14 John M, Kriebel–Schmitt R, Stauch M, et al. Weekly paclitaxel plus Herceptin® (trastuzumab) shows promising efficacy in advanced breast cancer. Breast Cancer Res Treat 2003;82:S49 (Abstract 221; poster update).
15 Gori S, Colozza M, Mosconi AM, et al. Phase II study of weekly paclitaxel and trastuzumab in anthracycline– and taxanepretreated patients with HER2–overexpressing metastatic breast cancer. BrJ Cancer 2004;90:36–40.
16 Gasparini G, Morabito A, De Sio L, et al. for the Herceptin Italian Trialist Group. Preliminary clinical results of a randomized phase IIB study of weekly paclitaxel (PCT) ± trastuzumab (T) as first–line therapy of patients (PTS) with HER2/neu positive metastatic breast cancer (MBC). Breast Cancer Res Treat 2003;82:S51 (Abstract 227; poster update).
17 Kuzur ME, Albain KS, Huntington MO, et al. A phase II trial of docetaxel and Herceptin in metastatic breast cancer patients overexpressing HER2. Proc Am Soc Clin Oncol 2000;19:131a (Abstract 512).
18 Toi M, Sasaki Y, Tokuda Y, et al. Phase I/II study of trastuzumab (Herceptin) on pharmacokinetics and safety in combination with paclitaxel or docetaxel for metastatic breast cancer. Ann Oncol 2002;13:51 (Abstract 182P).
19 Montemurro F, Choa G, Faggiuolo R, et al. A phase II study of three–weekly docetaxel and weekly trastuzumab in HER2–overexpressing advanced breast cancer. Oncology 2004;66:38–45.
20 Bauer-Kosi?nska B, Lema?nska I, Glogowska I, et al. Efficacy and toxicity of docetaxel or cisplatin chemotherapy in combination with trastuzumab in the treatment of patients with chemotherapy pre-treated HER/2 neu overexpressed metastatic breast cancer. Eur J Cancer 2003;1(Suppl.):S141 (Abstract 464).
21 Raab G, Brugger W, Harbeck N, et al. Multicenter randomized phase II study of docetaxel (DOC) given q3w vs q1w plus trastuzumab (TRA) as first-line therapy for HER2 overexpressing adjuvant anthracycline-pretreated metastatic breast cancer (MBC). Breast Cancer Res Treat 2002;76:S114 (Abstract 443; updated from poster).
22 Meden H, Beneke A, Hesse T, et al. Weekly intravenous recombinant humanized anti–Her2 monoclonal antibody (trastuzumab) plus docetaxel in patients with metastatic breast cancer (MBC): a pilot study. Proc Am Soc Clin Oncol 2001;20:60b (Abstract 1987).
23 Esteva FJ, Valero V, Booser D, et al. Phase II study of weekly docetaxel and trastuzumab for patients with HER2–overexpressing metastatic breast cancer. J Clin Oncol 2002;20:1800–8.
24 Extra et al. Eur J Cancer. 2004:125. Abstract 239.
25 Burstein HJ, Kuter I, et al. Clinical activity of trastuzumab and vinorelbine in women with HER2–overexpressing metastatic breast cancer. J of Clinical Oncology 2001, 19 2722–2730.
26 Jahanzeb M., Mortimer J.E., Yunus F., et al. Phase II Trial of Weekly Vinorelbine and Trastuzumab as First–Line Therapy in Patients with HER2+ Metastatic Breast Cancer. The Oncologist, Vol. 7, no. 5, 410–417, October 2002.
27 A. Chan et al. ASCO 2005, abstr. 587
28 Slamon DJ Update on Taxotere/Platinum/Herceptin combinations. 24th San Antonio Breast Cancer Symposium. 2001
29 Robert et al. Breast Cancer Res Treat. 2002;76:S37. Abstract 35.
30 Bangemann et al, ASCO 2005. Abstract 717.
31 Burstein HJ et al: Preoperative therapy with trastuzumab and paclitaxel followed by sequential adjuvant doxorubicin/cyclophosphamide for HER2 overexpressing stage II or III breast cancer. J Clin Oncol 21: 46–53, 2003.
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33 Harris LN, Burstein HJ: Preoperative trastuzumab and vinorelbine is a highly active, well-tolerated regimen for HER2+/FISH+ stage II/III breast cancer. Proc Am Soc Clin Oncol 22:22, 2003, abs 86.
34 Marty M, Cognetti F, Maraninchi D, et al. Efficacy and safety of trastuzumab combined with docetaxel in patients with HER2-positive metastatic breast cancer given as first-line treatment: results of a randomized phase II trial (M77001). J Clin Oncol2004.
35 Klein P, Gilkerson E. Patients with ER+/HER2+ or ER–/HER2+ tumours derive similar clinical benefit from trastuzumab (Herceptin®)–based therapy for metastatic breast cancer. Proc Am Soc Clin Oncol 2003;22:45 (Abstract 179).
36 Vogel CL, Murphy M, Cobleigh M, et al. Relationship of estrogen receptor (ER) status to clinical benefit in clinical trials of Herceptin®. Eur J Cancer 2001;37(Suppl. 6):S160 (Abstract 694).
37 De Laurentiis M, Arpino G et al. HER2 as a predictive marker of resistance to endocrine treatment for advanced breast cancer: a metanalysis of published studies. Breast Cancer Res Treat 2002; 76 (Suppl. 1): S 68.
38 Lipton A, Ali SM, et al. Elevated HER2/neu level predicts decreased response to hormone therapy in metastatic breast cancer. J Clin Oncol 2002; 20:1467–72.
39 Ellis M, Coop A, et al. Letrozole is more affective neoadjuvant endocrune therapy than tamoxifen for ErbB–1–and/or ErbB–2–positive, estrogen receptor–positive primary breast cancer: evidence from a phase III randomized trial. J Clin Oncol 2001; 19; 3808–16.
40 Wong ZW, Isaacs C, et al. A phase II trial of Letrozole and trastuzumab for ER and/or PgR HER2 positive metastatic breast cancer. Breast Cancer Res Treat 2003;82:S106, Abs 444.
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Standardized immunohistochemical study: receptor status in breast cancer (PR, ER, ki67, Her2 neu). It is performed only if there is a ready-made micropreparation on a slide and a tissue sample in a paraffin block.
Russian synonyms
IHC study (RE, RP, Her2/neu, Ki-67), immunohistochemical analysis of breast cancer receptor status.
English synonyms
IHC (ImmunoHistoChemistry) Test for Breast Cancer Receptor Status (ER, PR, HER2, Ki67), HER2 Overexpression by IHC, Estrogen Receptors, Progesterone Receptors, ER and PR Status, Estrogen and Progesterone Receptor Status.
Research method
Immunohistochemical method.
What biomaterial can be used for research?
Paraffin block with biopsy of breast formation. Primary tumor tissue can be obtained by core biopsy, as well as incisional and excisional surgery. To detect metastases, tissue from the wall can be taken for a biopsy chest, regional lymph nodes or distant organs.
General information about the study
Modern principles and strategies for the treatment of breast cancer are based, among other things, on the results of assessing the receptor status and proliferative potential of tumor cells. Tumor cells have the ability to produce and place on their surface special proteins - receptors, the stimulation of which leads to the launch of cell division and tumor growth. Such receptors are able to bind to substances that are normally present in the body and initially not associated with the development of a malignant neoplasm. According to current clinical guidelines, for breast cancer, the presence of the following receptors on tumor cells is important, various combinations of which are called receptor status:
Receptors for the hormones estrogen and progesterone er,PR). A significant proportion of breast tumors are hormone-dependent, that is, their growth is supported and stimulated by estrogens and progesterone. Tumors with a positive hormonal receptor status respond well to therapy with hormone analogues (tamoxifen), which block the corresponding receptors - bind to them, but do not cause activation of intracellular processes and prevent the receptor from subsequently binding to the hormone. Thus, the study of tumor production of ER and PR makes it possible to determine its sensitivity to these drugs.
Type 2 receptor for human epidermal growth factor receptor 2 HER2/neu). In the cells of some breast tumors, there is an increased production of this receptor protein, which, when combined with a natural growth factor, starts the process of division in the tumor cell. Total number of patients with HER2-positive breast cancer is from 15% to 20%. The determination of HER2/neu is not only of prognostic value (such tumors usually progress faster and have a more aggressive clinical development), but also allows us to assess the possibility of using targeted medicines- monoclonal antibodies to the HER2 receptor - trastuzumab (Herceptin), lapatinib, pertuzumab. In addition, HER2-positive tumors are resistant to tamoxifen.
Proliferative activity is an indicator of the ability of tumor cells for unlimited division, which is the main factor in the biological aggressiveness of a tumor. The process of division is accompanied by the appearance in the cell of certain proteins, one of which is Ki-67. It is not produced in cells at rest, which allows it to be used as a marker of tumor proliferative activity. Determining the level of Ki-67 has an important prognostic value, since tumors from the least mature and differentiated cells have the highest proliferative activity.
All of the above markers can be detected by immunohistochemical examination of the biopsy or surgical material of the tumor. For analysis from finished paraffin block using a special microknife, the thinnest sections are cut, which are then attached to glass slides and stained with routine dyes so that it is possible to distinguish cells from each other and from intercellular substance. Then the sections on the slides are stained with solutions of antibodies labeled with fluorescent labels specific to one of the studied receptors. If the desired receptor is present in the tumor cell, the antibodies bind to it, and when viewing the glass under a special microscope, fluorescence can be seen, which will indicate a positive test result. In addition, when viewing a section, a morphologist will be able to see that the stained marker is located in the nucleus, cellular substance, or on the membrane of tumor cells. The number of antibody solutions used corresponds to the number of markers that are examined in the sample. The degree of fluorescence and the percentage of cells in which it is present underlie the interpretation of the results of immunohistochemical analysis and are described in more detail in the corresponding section.
What is research used for?
- To determine the hormone receptor status and the degree of proliferative activity of breast cancer to assess the prognosis and individualization of treatment, including determining indications for the appointment of targeted therapy.
- Based on the results of the detection of hormonal receptors, the expediency of using antiestrogen is determined, and the HER2 receptor is determined by targeted anti-HER2 drugs. The revealed absence of these markers makes it possible to avoid prescribing obviously ineffective therapy. A high index of proliferative activity, as well as a negative receptor status, for the most part, is an indication for adding cytostatic drugs to the treatment.
When is the study scheduled?
- In the presence of histologically verified breast cancer - newly diagnosed, recurrent and metastatic tumors.
What do the results mean?
When interpreting the results of immunohistochemical determination receptor status of steroid hormones(estrogens and progesterone) in breast tumors, it is necessary to evaluate not only the percentage of cells stained with antibodies, but also the intensity of staining. Both of these parameters are taken into account in the Allred scale, where the percentage of positive cells is estimated from 0 to 5 points, and the intensity of staining is from 0 to 3. The sum of the two indicators is the final score, which determines the positivity of the tumor by receptor status: 0-2 negative, 3- 8 positive. An overall score of 3 on this scale corresponds to 1-10% of stained cells and is the minimum positive result when hormonal therapy can be effective.
Sometimes the receptor status is determined solely by the percentage of cells with stained nuclei. In such cases, NCCN recommends that all tumors with more than 1% positive cells be considered positive.
When interpreting color on receptorHER2/neu only membrane staining (staining of the cell membrane) is taken into account, which is evaluated on a scale from 0 to +3:
a result of 0 and +1 is considered HER2-negative;
2 - borderline result, with which, according to the immunohistochemical study, it is impossible to judge the presence of the HER2-neu receptor on the cell surface, a FISH or CISH study is necessary;
3 - positive result - targeted therapy with anti-HER2 drugs will be effective.
According to the classification of St. Gallen Consensus (2009), a low index of proliferative activity is considered level Ki-67 less than 15%, medium - 16-30%, and high - more than 30%.
What can influence the result?
- The quality of the paraffin blocks provided, the experience and qualifications of the pathologist, since the immunohistochemical method is not fully standardized and the evaluation of its results is somewhat subjective.
- The interpretation of the results of the study should be carried out exclusively by a doctor of the relevant specialty, the data on the effectiveness and expediency of prescribing certain drugs, depending on the results of the study, are purely advisory in nature and can be revised taking into account the individual characteristics of the patient.
Important Notes
- In case of uncertain HER2/neu-receptor status (the result of immunohistochemical study 2+), it is recommended to perform a FISH- or CISH-study, which will reveal hyperactivation of the gene encoding this receptor. If these studies are unavailable, a second immunohistochemical study is allowed, but on a different sample of tumor tissue.
- There are several scales for assessing the receptor status of breast cancer, the laboratory report should indicate which one was used to evaluate the positivity of the tumor in this study, as well as a descriptive characteristic of the number of positive cells, staining features of cellular structures and morphological features of cells.
Histological examination of the biopsy material of the formation of the mammary gland
Cytological examination of breast punctures
Determination of HER2 tumor status by FISH
Determination of HER2 tumor status by CISH
Who orders the study?
Oncologist, mammologist, oncogynecologist.
Literature
Dana Carmen Zaha. Significance of immunohistochemistry in breast cancer. World Journal of Clinical Oncology, 2014; 5(3): 382-392.
NCCN Clinical Practice Guidelines in Oncology: Breast Cancer. Version 3.2017 – November 10, 2017. Available at www.nccn.org.
Clinical laboratory diagnostics: national leadership: in 2 volumes - T. I / Ed. V. V. Dolgova, V. V. Menshikov. - M.: GEOTAR-Media, 2012. S. 658-660.
V. F. Semiglazov, R. M. Paltuev, V. V. Semiglazov, G. A. Dashyan, T. Yu. Semiglazova, P. V. Krivorotko, K. S. Nikolaev. General recommendations for treatment early cancer mammary gland Galle-2015, adapted by the experts of the Russian Society of Mammary Oncologists. Tumors of the female reproductive system, 2015; 3:43-60.
Questions: 167
Hello! My mom had surgery to remove right chest. Received the results of the study. Please help me to decipher. Thanks. Immunohistochemical study of tumor tissue: estrogen receptors 6 points (D.C. Allred scale), clone SP1 (Thermo Fisher-Labvision); progesterone receptors 4 points (D.C. Allred scale), clone PgR YR 85 (Thermo Fisher-Labvision); the result of c-erbB-2 oncoprotein HER 2 heu (clone SP 3 Thermo Fisher-Labvision) - 0 points (negative).
Answers the question: Krasnozhon Dmitry Andreevich
Hello Olga. You only provided data. According to these data, the tumor is hormone-dependent and insensitive to targeted therapy. To talk about the prognosis and treatment, you also need to know the index of proliferative activity (ki67), the stage of breast cancer. In any case, you should be guided by the opinion of the attending physician.
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Good afternoon, Dmitry Andreevich. I had a sectoral resection of the left breast. Histological tests showed G2. After 2 weeks, the histology was redone in another laboratory with a High-Grade result. Analyzes IHC ER 80%, PR 7%, Her-2neu 1+, Ri67 30%. According to the ultrasound results, the lymph nodes are unchanged, but there is a fibroadenoma and a cyst in the operated left mammary gland. Also, osteoscinography was done. No pathological foci have been identified. I would like to know what these results mean and whether it is necessary to completely remove the breast and lymph nodes?
Answers the question: Krasnozhon Dmitry Andreevich
Hello, Natalia. To determine the stage of breast cancer, you need to know the size of the tumor. If the tumor size is up to 2 cm and the lymph nodes are not affected, and there are no signs of local spread of the tumor, then we will talk about stage 1 breast cancer. In such cases, it is necessary to conduct an examination - computed tomography organs of the chest and abdominal cavity, bone scintigraphy, establish the stage of breast cancer and then plan treatment. I in a similar case would begin treatment with operation - organ-preserving or - it is necessary to discuss a question at internal consultation. After a radical operation, I would prescribe chemotherapy (4 AS - doxorubicin and cyclophosphamide and 4 courses of paclitaxel in mono regimen once every 3 weeks), after chemotherapy I would prescribe hormone therapy.
More information is needed to discuss the situation in more detail.
In any case, you should be guided by the opinion of the attending physician.
I think that you will be interested in my book "Breast Cancer. Answers to Questions", which can be obtained with any order from 3 thousand rubles in the Bintoff.Ru online store (http://www.bintoff.ru) or directly in the store when ordering from 3 thousand rubles (St. Petersburg, Elizarovskaya st. 41, office 218). The book can always be obtained from the department where I work. To do this, you just need to come on Wednesday after 4 pm, contact me and without any conditions I will give it to you.
Good afternoon, Dmitry Andreevich. I had a sectoral resection of the left breast. For histological examination, ki 67 analysis was not recommended, why, because this is one of the key indicators? Thanks.
Answers the question: Krasnozhon Dmitry Andreevich
Hello Ludmila. When diagnosing breast cancer, we always prescribe a complete immunohistochemical study. Another thing is that ki67 is not performed in our laboratory and patients need to pay for this study in a commercial laboratory. In any case, you should be guided by the opinion of the attending physician.
Hello, Dmitry Andreevich! I am writing to you again. Thanks a lot for your answers! I'm 35 years old. In 2016, BC was diagnosed. IIc T2N1M0. Removed 2 tumors in one mammary gland. According to the results of histology, made in RKOD Ufa IHC 1 tumor: Er(+++) H=220 (Allred 8b), PR(-) H=0, Her2neu(+) neg. status, Ki67 2%, 2 tumors: Er(-) H=0, Pr(0)H=0 Her2neu(+++) positive status, Ki67 up to 45%. It was recommended to bring glass and blocks to another region. According to the results of histology made in the RKOD Kazan IHC 1 tumor: HER2-positive status (+++), BenchMark Ultra, Er=0, Pr=0, ki67 index up to 40%, 2 tumors: HER2-positive status (+ ++), BenchMark Ultra, Er=0, Pr=0, ki67 index up to 45%. They were treated only as HER: 4 courses of chemotherapy according to the AC regimen (doxorubicin + cyclophosphamide) before surgery, 4 courses of chemotherapy in DH mode (docetaxel + transtuzumab) after surgery, then radiation and transtuzumab 1 year after surgery (19 injections in total). Now the treatment is over, I do not take anything. But I am concerned about the question, what if the first analysis was still correct and one tumor is hormone-dependent, and I do not take tamoxifen. Maybe it's worth double-checking the analysis in Moscow (at the P. A. Herzen Moscow Research Institute or the N. N. Blokhin Russian Cancer Research Center)? Please advise!
Doctor, hello. Breast cancer, with the initial trepan biopsy ki67, for some reason, was not counted. They just wrote "high" The value of this parameter (=10%) was determined only from materials taken during mastectomy. Before the mastectomy, 6 sessions of chemotherapy were made according to the AC scheme. The question is: could ki67 decrease from chemotherapy? Or was it like that in the beginning? I would be very grateful for the answer, I would like to better understand my illness. Thanks! Best regards, Olga, Moscow
Answers the question: Krasnozhon Dmitry Andreevich
Hello Olga. Immunohistochemical data , including ki67 data , may differ when examining a tumor before treatment and after chemotherapy . I would be guided by the data obtained before chemotherapy.
Hello, Doctor! In breast cancer, when there are 99% receptors for estrogen and 65% for progesterone, should homonotherapy be carried out or is it better to remove the ovaries.?
Answers the question: Krasnozhon Dmitry Andreevich
Hello Khadija. To answer your question, you need to know the stage of breast cancer. If we are talking about stage 3 breast cancer, then I would consider removing the ovaries and prescribing tamoxifen. If we are talking about stages 1-2, then most likely I would prescribe only tamoxifen. Once again I repeat - you need to know a lot of details in order to argue on this topic. Look at the answers to questions about hormone therapy, about tamoxifen,. In any case, you should be guided by the opinion of the attending physician.
Dmitry Andreevich, hello. My name is Tatyana. Cancer of the left breast, stage 2b. I had an operation (mastectomy). By IHC analysis to hormones progesterone+, to estrogen-. Progesterone percentage is not specified. I was prescribed tamoxifen. How effective is hormone therapy in this case? I want to hear your opinion. Thank you in advance.
Answers the question: Krasnozhon Dmitry Andreevich
Hello Tatiana. Usually, an immunohistochemical study indicates either a percentage, or points, or units (hscore). Hormone therapy is effective in hormone-dependent breast cancer. In stage 2b, chemotherapy is usually prescribed after radical surgery. It is also important to understand what the index of proliferative activity is, and it is also important to know whether the tumor is sensitive to targeted therapy or not. In any case, you should be guided by the opinion of the attending physician.
Hello! Received today the results of a trephine biopsy of the breast. In conclusion - invasive cancer, G1, er100%, pr70%, ki 67 10%, her neu0 (sorry, I write from memory, the numbers are the same, maybe I'm wrong with the names). I'm 43 years old. Cancer was found in the area of postoperative scar from purulent mastitis, which was 19 years ago. On elastography, the area of increased rigidity is about 2 cm, on mammography - the area of restructuring is 1.3 by 1.3 cm. Tell me, what can be the prognosis for my type of cancer, do I have a chance for recovery and what treatment regimen should I use? Thank you in advance for your reply.
Answers the question: Krasnozhon Dmitry Andreevich
Hello Antonina. According to the immunohistochemical study, the tumor is hormone-dependent, the proliferative activity index is low, the tumor is insensitive to targeted therapy (trastuzumab, pertuzumab). If we are talking about stage 1, then after breast cancer (surgery + hormone therapy), the prognosis will be favorable and you will no longer encounter this disease. You need to supplement the examination in order to exclude distant metastases (X-ray of the lungs, ultrasound of the abdominal cavity, at least). In any case, you should be guided by the opinion of the attending physician.
I think that you will be interested in my book "Breast Cancer. Answers to Questions", which can be obtained with any order from 3 thousand rubles in the Bintoff.Ru online store (http://www.bintoff.ru) or directly in the store when ordering from 3 thousand rubles (St. Petersburg, Elizarovskaya st. 41, office 218). The book can always be obtained from the department where I work. To do this, you just need to come on Wednesday after 4 pm, contact me and without any conditions I will give it to you.