Breast cancer treatment in Israel is internationally recognized for its exceptional quality, advanced medical technologies, and highly skilled oncology specialists. This comprehensive guide provides detailed information about breast cancer epidemiology, diagnosis, and state-of-the-art treatments available in Israeli medical centers.
Breast cancer
Breast cancer is a tumor that usually originates in the milk ducts that carry milk to the nipple, or in the lobules that contain the glands that produce milk.
Most malignant tumors in the breast are carcinomas. The tumor can be invasive, meaning it breaks through the ducts into the breast tissue, or non-invasive – limited to the ducts only without breaking through the breast tissue.
Breast cancer is the most common malignant tumor in women, accounting for about a quarter of all cancer cases. It is estimated that one in eight women will develop breast cancer during her lifetime.
Breast Cancer Statistics and Epidemiology
Breast cancer is the most common malignant tumor in women, accounting for about a quarter of all cancer cases. The rate of men with the disease is only about 1% of all cases.
In the second half of the twentieth century, there was an increase in the incidence of the disease. In Israel, approximately 4,000 new cases of breast cancer are diagnosed each year, of which 5-10% are detected in the metastatic stage.
Causes and Risk Factors of Breast Cancer
The etiology of most breast cancer cases is unknown.
However, several factors have been found to be associated with an increased risk of developing the disease:
- Age – the risk of developing cancer increases with age. Data shows that breast cancer is more common among women aged 50 and over, approximately 76% of patients are diagnosed in these ages. Approximately 17% of patients are diagnosed between the ages of 40-49, and approximately 6% of patients are younger than 40 at the time of diagnosis.
- Family history of breast cancer at a young age.
- Past breast cancer.
- First menstruation at an early age (before age 11)
- Entering menopause at a relatively late age (after age 55)
- Women who have never given birth, or first birth at an older age.
- Lifestyle – Recent studies indicate a clear link between increased risk of the disease and obesity and lack of physical activity. Certain studies have indicated, for example, an increased risk of the disease as a result of excessive alcohol consumption, high fat intake and excess calories, and more.
Approximately 10% of women have a specific genetic defect that significantly increases the risk of developing breast cancer. This defect is suspected when there is a family history of breast or ovarian cancer, especially in first-degree relatives: a mother or sister. Not all genetic defects are identified, but in approximately 5% of women, breast cancer appears due to a genetic defect in the genes called BRCA2 (Breast cancer 2 gene) and BRCA1 (Breast cancer 1 gene). Among women who are carriers, the risk of developing breast cancer is approximately 50-80%, compared to approximately 12% in the general female population. Despite this, most women diagnosed with breast cancer do not have a family history of this disease.
Clinical Presentation and Types of Breast Cancer
Stages of the disease
The extent of the spread of the disease (Staging) is graded according to 3 characteristics:
- T – The extent of penetration of the primary tumor
- N – The number of lymph nodes involved
- M – The presence of distant metastases
In addition to determining the type of tumor and the extent of its spread, the grade of the tumor is also examined histopathologically.
This grade is determined by evaluating the morphological characteristics of the tumor: the formation of tubules, nuclear pleomorphism, and mitotic division. Grade 1 has the best prognosis and grade 3 has the worst prognosis.
The presence and amount of estrogen, progesterone, and HER2 (Human epidermal growth factor receptor 2) receptors are also examined. This information is important both in assessing the risk of disease recurrence and in determining subsequent treatment.
Malignant Breast Tumors
Most breast tumors are carcinomas. The tumor can be invasive, meaning it breaks through the ducts into the breast tissue, or noninvasive – limited to the ducts only without breaking through the breast tissue.
Common Subtypes
– Noninvasive Breast Cancer
- Ductal Carcinoma in Situ (DCIS)
– Invasive Breast Cancer
- Invasive Ductal Carcinoma – originates in the milk ducts. It accounts for about 85% of all breast carcinomas.
- Invasive Lobular Carcinoma – originates in the glands where milk is produced.
– Rare subtypes
- Paget’s disease of the breast – manifests as a kind of eczema of the skin around the nipple, and sometimes there is also a malignant lump in the breast itself.
- Inflammatory breast cancer – a generalized process in the breast, without a defined lump, which appears as acute inflammation with redness, local heat and swelling of the breast.
Another rare type of breast tissue tumor that is not carcinoma is sarcoma and originates in the connective tissue.
Diagnosis and Early Detection of Breast Cancer
Early detection and guidelines for screening tests
Early detection is the most effective means of curing breast cancer. The chances of curing a disease diagnosed at an early stage increase to about 90% or more.
Manual breast examination
Breast cancer can be detected with the help of manual self-examination, a doctor’s examination or imaging. In the past, self-examination of the breast was recommended once a month as part of a follow-up routine. Today, this recommendation is not valid, but awareness and vigilance for changes in the breast are definitely recommended, and seeking medical examination and advice if there is a concern about a change or finding in the breast.
An annual breast examination by a doctor experienced in breast examination is recommended starting at age 40.
Mammography
The National Oncology Council in Israel recommends mammography examinations for women:
- From age 50 and older, every two years, or as recommended by the attending physician. The need for screening is particularly emphasized for women of this age group, for whom there is now international professional consensus that mammography helps diagnose the disease in its early stages and reduces mortality from breast cancer.
- For women in a risk group, with a family history – a mother or sister who has had breast cancer – it is recommended to undergo screening once a year, between the ages of 40-49.
Mammography is effective in 80-90% of cases. It is the best test for early detection. Mammography is superior to other existing tests, ultrasound, and magnetic resonance imaging (MRI); it is the only one that has been shown to reduce mortality by about 30%. Younger women must receive a special medical referral to have this test performed. Under the age of 50, the breast structure is usually still dense and thick and there is hormonal activity that makes it difficult to detect changes in the breast on a mammogram.
In women with a significant family history of breast cancer and carriers of a mutation in the BRCA1 or BRCA2 genes, it is recommended to begin clinical and imaging follow-up at a young age (25-30) and to perform breast imaging by MRI. MRI is included in the health basket for carriers and women with a significant family history of breast cancer.
Diagnosis
After a finding is discovered in the breast, a biopsy will be performed, which will be sent for pathological examination and will allow a diagnosis of whether it is a malignant tumor.
Breast Cancer Treatment Options in Israel
Breast cancer treatment components
- Surgery – more common in early breast cancer, to remove the primary tumor and sample or remove the axillary lymph nodes. Rarely, surgery will be performed to remove metastases.
- Radiation – given as adjuvant therapy for patients with early breast cancer and as palliative therapy for patients with metastatic breast cancer.
- Chemotherapy – given as a treatment for active disease or as a preventive treatment. There is a wide variety of chemotherapies that are given as a single treatment or in combination with two or more drugs (combination therapy). The patient usually receives several cycles of treatment, with each treatment cycle usually lasting two or three weeks, depending on the protocol chosen. Most chemotherapies are given intravenously. There are also oral medications such as Xeloda (Capecitabine), Vinorelbine, and Endoxan (Cyclophosphamide).
- Hormonal therapy – Hormonal therapies are given to patients with tumors that are positive for estrogen and/or progesterone receptors. Hormonal therapies can be divided into several groups:
- Antiestrogens
- Aromatase inhibitors
- Pure antiestrogens from the SERD (Selective estrogen receptor down-regulator) group
- Progestins
- Estrogens
- Androgens
- Targeted (biological) therapy – These therapies are directed against processes unique to the tumor and include two groups:
- Small molecules – Tyrosine kinase inhibitors. These molecules penetrate the interior of the cancer cell and inhibit enzymatic processes related to cell proliferation.
- Monoclonal antibodies – proteins produced by genetic engineering. The antibodies specifically target proteins that are overexpressed on the surface of the malignant cell membrane, inhibiting their growth and activating the body’s immune system against them.
Early Breast Cancer Treatment
Early breast cancer is defined as a tumor that has not yet metastasized and is no larger than 5 cm. Spread to the lymph nodes does not indicate metastatic breast cancer. These are stages 0, 1, and 2.
In early disease, the standard treatment is surgery, with the type of surgery and the need for additional treatment determined based on the size of the tumor and its characteristics. Additional treatment can include a combination of radiation, chemotherapy, biological therapy, and hormonal therapy. The goals of treatment in the early stage are to cure the disease and reduce the rate of its recurrence.
Radiation therapy is given as a treatment that complements local treatment after surgery. Its goal is to prevent local-regional recurrence of the tumor, mainly in women who have undergone partial resection (lumpectomy), and sometimes even after complete resection (mastectomy). The series of treatments is given over a period of about 5-7 weeks. Today, shorter radiation protocols can also be given, and in selected cases, intraoperative radiation therapy) which eliminates the need for breast irradiation after surgery.
Chemotherapy
Chemotherapy is given to prevent recurrence of the disease. It is usually given after surgery. There are cases in which it is given before surgery in order to reduce the size of the tumor and improve the surgical result. Usually, the treatment protocol will include different phases, which are usually given in cycles of every two or three weeks. The duration of treatment is determined by the chosen treatment protocol.
Examples of chemotherapy treatment for early disease:
- Doxorubicin in combination with Endoxan
- Doxorubicin in combination with Endoxan, followed by Paclitaxel
- Docetaxel in combination with Endoxan
Adjunctive hormonal therapy
Adjunctive hormonal therapy is selected according to the woman’s age, the stage of the disease, her medical profile and the decision of the doctor and the patient.
The treatment is usually given for a long period, of five years or more, and includes the following:
- Antiestrogens – Tamoxifen.
- Aromatase inhibitors – such as Letrozole, Anastrozole and Aromasin (Exemestane).
- Ovarian ablation or suppression.
Biological therapy
In disease in which there is overexpression of the HER2 protein, the treatment regimen also includes treatment for a year with the monoclonal antibody Herceptin (Trastuzumab) that opposes the activity of the HER2 protein.
In cases where there is overexpression of HER2, the accepted chemotherapy protocols are:
- Doxorubicin and Endoxan, followed by Paclitaxel and Herceptin, then Herceptin alone
- Docetaxel, Carboplatin and Herceptin, followed by Herceptin alone
Treatment of locally advanced breast cancer
Locally advanced breast cancer (stage III) is an invasive breast tumor that is larger than 5 cm and significantly involves the lymph nodes, with a fixed lymph node mass in the armpit. These tumors are divided into the following subgroups:
- Tumors for which an initial surgical approach is possible: Stage T3N1M0. These tumors will be given adjuvant radiation and systemic therapy (chemotherapy, hormonal, biological) after surgery, similar to early breast cancer. Sometimes, initial chemotherapy will be given in order to reduce the tumor and allow breast conservation.
- Tumors for which an initial surgical approach is not possible: These tumors are included in stages IIIA (excluding T3N1M0), IIIB and IIIC. In these tumors, the standard of care is preoperative chemotherapy. In tumors that express more HER2, anti-HER2 therapy will be combined already at this stage.
After chemotherapy, local treatment will be performed, including surgery and radiation.
Adjuvant systemic treatment after surgery will include hormonal and anti-HER2 therapy depending on the characteristics of the tumor.
Treatment of advanced breast cancer
Advanced breast cancer (stage 4) is a tumor of any size that has metastasized to distant parts of the body. The most common sites of metastasis are: bones, lungs, pleura, liver, skin, glands, and brain.
Currently, metastatic disease is incurable. The goal of treatment is to relieve symptoms, control the disease, and improve the patient’s quality of life.
The main treatment for metastatic breast cancer is systemic treatment using chemotherapy, hormonal or biological therapy, or a combination of them. In some cases, targeted radiation therapy will also be given as palliative treatment, for example in cases where there are metastases in the bones or brain.
Systemic therapy in the metastatic stage is usually continued until disease progression or treatment-limiting toxicity occurs. After disease progression, systemic therapy is replaced by another therapy, and so on.
Hormonal therapy
Hormonal therapy is given to patients whose disease is estrogen and/or progesterone receptor-positive, and whose disease is not aggressive and does not require an immediate response to treatment.
Common hormonal therapies for metastatic disease include ovarian suppression if necessary, aromatase inhibitors (such as Letrozole, Anastrozole, and Aromasin), antiestrogens (Tamoxifen), pure antiestrogens from the SERD group, such as Faslodex (Fulvestrant), and drugs from other groups as listed above.
These treatments can be given as a single treatment or in combinations. After the disease progresses during a given treatment, it is possible to switch to another hormonal treatment from the same group or from other groups depending on the patient’s condition and the nature of the disease.
Chemotherapy
Chemotherapy is given as initial treatment for metastatic disease for patients whose disease does not have positive estrogen and/or progesterone receptors, or in situations where a rapid response to treatment is required – involvement of internal organs, rapidly progressing disease, severe symptomatic disease, etc.
Chemotherapy will also be given in cases where the patient has been treated with several hormonal lines and no longer responds to this type of treatment. Most often, the treatment will be given as a single chemotherapeutic agent and not as combinations of several chemotherapy drugs, despite the increased effectiveness, since the administration of several drugs involves toxicity and impairment of the patients’ quality of life.
After the disease progresses with a given line of treatment, it is possible to switch to another type of chemotherapy. There is variability in response to the various chemotherapy treatments, and the treatment decision refers to both the expected efficacy of the treatment and the side effect profile and previous treatments that the patient has received.
Examples of common chemotherapy drugs given by infusion:
- Anthracyclines, such as Doxorubicin
- Taxanes, such as Paclitaxel or Docetaxel
- Gemcitabine
- Vinorelbine
- FU-5 (Fluorouracil-5)
- Endoxan
Examples of common chemotherapy drugs given orally:
- Xeloda
- Vinorelbine
Biological therapy
Depending on the characteristics of the tumor, drugs with targeted biological activity can be combined in the treatment regimen. In disease with overexpression of HER2, anti-HER2 therapy will be combined with chemotherapy or hormonal therapy.
It is also common practice to continue anti-HER2 therapy, such as Herceptin or Tykerb (Lapatinib), even after disease progression, while replacing chemotherapy. In disease that does not overexpress HER2, the angiogenesis inhibitor Avastin (Bevacizumab) can be combined with paclitaxel chemotherapy as first-line treatment.
Breast Cancer Drug Treatments
Xeloda
Mechanism of Action
Xeloda is a chemotherapy that is given in oral tablets, so that hospitalization can be avoided, and the patient can receive the treatment at home.
Xeloda contains the substance FU-5, a long-standing chemotherapy substance known in cancer treatment.
FU-5 can be treated in its original form by intravenous infusion only. Xeloda contains the substance FU-5 in an inactive form, so that it can be taken orally.
The drug is absorbed in the intestine as an inactive substance, reaches all tissues of the body through the bloodstream and undergoes decomposition by the enzyme thymidine phosphorylase, which is mainly found in tumor cells, and makes the substance active.
Due to Xeloda’s unique mechanism, which activates the drug mainly in tumor cells, the drug mainly damages tumor cells and its side effects in other organs of the body are relatively few compared to other chemotherapies.
Efficacy
The efficacy of Xeloda in the treatment of metastatic breast cancer has been consistently demonstrated in many studies. Xeloda is the treatment of choice in patients who have been treated with taxane and anthracycline chemotherapy or in patients who are not suitable for treatment with these drugs.
Xeloda as single therapy
In a phase III clinical study, 325 women were randomly assigned to one of two first-line treatment arms for metastatic breast cancer: a CMF (cyclophosphamide methotrexate and 5-FU combination chemotherapy) arm, and a Xeloda arm.
Xeloda was found to reduce the risk of death by 28% compared with CMF, with median overall survival being 22 months in Xeloda patients compared with 18 months in CMF patients.
A retrospective analysis published in 2004 found that treatment with Xeloda, compared with other chemotherapy, significantly extends the median survival of patients with metastatic breast cancer from approximately 12 months to 21 months.
Xeloda as part of a treatment combination
Adding Xeloda to Taxotere in the first-line treatment line significantly extends survival by approximately three months from 11.5 months to 14.5 months, and also increased the percentage of women responding to treatment – 30% in the Taxotere single-agent treatment arm compared to 42% in combination with Xeloda.
Herceptin
HER2-positive breast cancer: In approximately 20% of women with breast cancer, the tumor is defined as HER2-positive. This type of tumor is characterized by an aggressive course of the disease and a poor prognosis compared to other types of breast cancer.
The use of Herceptin has led to a significant improvement in the prognosis of these patients, which is now better than that of other patients.
Mechanism of action
Herceptin is the first treatment against an oncoprotein that has been shown to improve survival in breast cancer patients.
Herceptin is a monoclonal antibody that specifically targets the HER2 receptor, which plays a central role in transmitting signals that promote cell growth and division in the body.
In HER2-positive breast cancer, there is an amplification of the gene encoding this protein, which causes overexpression of HER2 on the surface of the tumor cells, resulting in their uncontrolled proliferation.
Herceptin selectively binds to HER2 in tumor cells and prevents its activity, thereby inhibiting tumor growth and spread in the body.
A tumor is defined as HER2-positive when overexpression of the protein is detected by immunohistochemistry and/or amplification of the HER2 gene by FISH (fluorescence in situ hybridization).
A patient is eligible for Herceptin treatment if the immunohistochemistry is graded as 3+ or when the FISH test is positive.
Efficacy of Herceptin in early breast cancer
Herceptin treatment has proven highly effective in women with HER2-positive breast cancer.
In patients with early-stage disease, a reduction in the rate of disease recurrence and a reduction in mortality have been demonstrated.
Four large studies, including more than 13,000 patients, have demonstrated the efficacy of Herceptin for one year in combination with chemotherapy (compared to chemotherapy alone) as adjuvant treatment for HER2-positive early breast cancer.
A pooled analysis of two of the studies, the National Surgical Adjuvant Breast and Bowel Project (NSABP B-31) and the North Central Cancer Treatment Group (NCCTG N-981), demonstrated that adding Herceptin to chemotherapy reduced the risk of disease recurrence by 52% with a hazard ratio (HR) of 0.48, and reduced the risk of death by 33% (HR-0.67) at a median follow-up of 24 months.
A calculation based on the results of the four studies found that, thanks to Herceptin treatment, the lives of nearly 28,000 early breast cancer patients in the five largest European countries will be saved over 10 years.
Herceptin is recommended in international guidelines, including the NCCN (National Comprehensive Cancer Network) recommendations in the United States and the NICE (National Institute for Health and Clinical Excellence) recommendations in the United Kingdom, as the standard of care for patients with HER2-positive early breast cancer.
Herceptin efficacy in metastatic breast cancer
In patients with advanced disease, it has been shown to prolong patient survival and improve response rates to treatment:
- Herceptin in combination with chemotherapy
The pivotal study H0648g included 469 women with HER2-positive metastatic breast cancer, who were randomized to receive Herceptin in combination with chemotherapy, or chemotherapy alone.
This study demonstrated that the addition of Herceptin significantly improved the response rate to treatment (56% vs. 31%) and the median survival of patients (29 vs. 20 months). Additional studies were subsequently performed that demonstrated significant benefit when Herceptin was added to standard chemotherapies.
- Herceptin as single therapy
A study by Vogel et al included 114 patients with HER2-positive metastatic breast cancer who were treated with Herceptin as a single agent in first-line therapy. In patients with immunohistochemistry 3+ (+IHC3), a response rate of 35% and a median survival of 24.5 months were demonstrated.
- Herceptin as continued treatment after disease progression
A study by the German breast group (GBG) included 156 patients with HER2-positive metastatic breast cancer whose metastatic disease progressed during treatment with Herceptin and as first-line therapy.
The women were randomized to one of two treatment arms: continuation therapy with Herceptin in combination with Xeloda, or Xeloda alone. The results of the study showed that continued administration of Herceptin significantly improved the response rate to treatment (48.9% vs. 24.6%) and prolonged the time to disease progression (8.2 vs. 5.6 months).
Following the results of this study and other studies, the current accepted approach is to continue blocking HER2 receptor activity throughout the course of the disease, while replacing the chemotherapy component given in the combination.
- Herceptin in combination with hormonal therapy
In the TANDEM 208 (Trastuzumab and Anastrozole directed against ER-positive) study, patients with HER2-positive and estrogen- and progesterone-receptor-positive metastatic breast cancer were randomized to receive Herceptin in combination with an aromatase inhibitor or an aromatase inhibitor alone as first-line therapy. The addition of Herceptin improved the response rate to treatment (20.3% vs. 6.8%) and doubled the time to disease progression compared with hormone therapy alone (4.8 vs. 2.4 months).
Avastin
Mechanism of action
The formation of new blood vessels (angiogenesis) is a process that allows malignant tumors to receive oxygen and nutrients, and is therefore essential for their growth and metastasis to distant organs.
This process is activated by the tumor through the secretion of the protein VEGF (vascular endothelial growth factor).
The new blood vessels that form differ in their structure and properties from mature blood vessels, and their survival depends on the continued presence of VEGF. Elevated levels of VEGF have been demonstrated in various malignancies such as colon, breast, lung and brain, and their level has been found to correlate with poor prognosis.
Avastin is the first drug to enter clinical use that acts by inhibiting angiogenesis.
It is a monoclonal antibody that specifically binds to VEGF. This binding prevents it from binding to receptors on the surface of endothelial cells and activating them, thus inhibiting the process of angiogenesis. In addition, Avastin improves the delivery of chemotherapy to the tumor by reducing the high permeability that characterizes the blood vessel wall formed during the angiogenesis process. The damage to the blood supply to the tumor and the improvement of the delivery of chemotherapy to it cause its regression and limit its spread in the body.
Avastin is the only anti-angiogenic treatment approved for the treatment of breast cancer.
Efficacy
A phase III study that included 722 patients with metastatic or locally recurrent HER2-negative breast cancer examined the efficacy of Avastin in combination with paclitaxel chemotherapy compared with paclitaxel alone as first-line treatment.
Combination therapy with Avastin doubled the median time to progression (PFS) to 11.8 months, compared to 5.9 months with chemotherapy alone, with a 40% reduction in the risk of disease progression (HR=0.6) compared to chemotherapy alone. In addition, the addition of Avastin doubled the proportion of patients who responded to treatment (50% vs. 25%).
The efficacy of Avastin was demonstrated in the different subgroups of the study regardless of patient age, hormone receptor status, prior exposure to chemotherapy in early-stage disease, etc. Avastin, in combination with Paclitaxel, is recommended in the NCCN guidelines for the treatment of recurrent or metastatic breast cancer.
In Israel, Avastin is registered for the treatment of metastatic breast cancer patients as a first-line treatment in combination with Paclitaxel.
Breast Cancer Prognosis and Survival Rates
Treatment and prognosis according to disease stages
Why Choose Israel for Breast Cancer Treatment?
Patients choosing Israel benefit from advanced diagnostic methods, personalized treatment protocols, innovative clinical research, multidisciplinary medical teams, and comprehensive patient support services. Israeli hospitals are at the forefront of oncology, frequently pioneering breakthrough treatments.
Take the First Step Towards Recovery
If you are looking for advanced and personalized breast cancer treatment in Tel Aviv, Israel, our medical center offers state-of-the-art diagnostic methods and treatment protocols tailored to your needs.
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