الفهرس 
INTRODUCTIONOnly 14 pages are availabe for public view
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Abstract
Metastatic breast cancer is defined by tumor spread beyond the breast, chest wall, and regional lymph nodes. The most common sites for breast cancer metastasis include the bone, lung, liver, lymph nodes and brain. MBC can be presented either as; denovo MBC or recurrent MBC after treatment.
The primary goals of treatment in MBC are maximizing the quality of life, palliation of symptoms and prolongation of survival. Treatment choice should also take into account important factors such as; physiologic age, performance status, co-morbidities, menopausal status, previous therapies, disease-free interval, number and site of metastases, the need for a rapid disease/symptom control and, receptor status; ER, PR and HER2
Since endocrine therapy alone or in combination with targeted agents is generally less toxic than chemotherapy, it is preferable for most patients with HR+/Her2- disease to begin treatment with endocrine therapy (ET), reserving chemotherapy for patients whose cancers appear to be either refractory to ET or have extensive symptomatic visceral involvement. Several studies have suggested that addition of targeted therapies to ET improves PFS, although OS results from several studies are still pending. These agents include mTOR inhibitors, CDK 4/6 inhibitors and PI3K inhibitors.
Regarding HR+/Her2+ MBC patients, HER2-directed therapy is recommended as first- and later-line treatment with chemotherapy or endocrine therapy. Multiple HER2- directed agents are available for use such as; trastuzumab, pertuzumab, ado-trastuzumab emtansine (T-DM1), fam-trastuzumab deruxtecan, tucatinib, lapatinib, and neratinib.
The first part of this study was conducted in a retrospective manner and included 611female patients with metastatic breast cancer either denovo or recurrent (HR positive and Her2 positive or negative) who were diagnosed and treated at ACOD during the period from January 2010 to December 2019 aiming for descriptive analysis of the types of systemic treatment received by metastatic HR positive breast cancer patients to review the change in treatment pattern during the last 10 years and to compare between the efficacy of chemotherapy and endocrine therapy in terms of overall survival, progression free survival, response rate and the reported, toxicity of each type of systemic therapy for women with HR positive MBC.
The studied patients included premenopausal and postmenopausal women with mean age of 50 years. 426 patients (68.4%) weren’t metastatic from the start and received previous locoregional treatment and 185 patients (31.6%) were metastatic from the start. The previous chemotherapy that received in (neo)adjuvant setting in recurrent MBC patients, 53.9% patients received anthracycline based only, 13.9% patients received anthracycline and taxanes. 72.3% received adjuvant tamoxifen with median duration was 2 years.
Pathology of surgery in cases when locoregional treatment received, IDC was the most common histologic type seen in 381 patients (79.5%) with Grade 2 constituting 62% of total. Variability existed among patients regarding the tumor size and number of involved lymph nodes and the classification was based upon pathologic criteria after surgery on diagnosis
Frequency of bone metastases as initial presentation 64.2%, locoregional recurrence 43.5%, lung 39.3%, liver 27.3%, brain 5.2%. Out of 611 studied patients, 70 patients (11.4%) presented initially with visceral crisis. 312 (51.1%) patients have lost follow-up either before starting treatment, after first or subsequent lines of treatment, 33.6% patients died and 15.4 % survived.
As a first line systemic therapy, chemotherapy was offered to 390 studied patients (63.8%). But, hormonal treatment was offered to 188 patients (38.2%) with significant change in the choice of first line therapy between first 5 and the last 5 years. As a second line systemic therapy, hormonal therapy was administered to most patients in the second line. When selecting patients who were hormone receptor positive Her2 negative with no visceral crisis initially, the first line chemotherapy was offered to 56.7% of those patients with significant change in trend of first line treatment choice between the first 5 years and second 5 years.
Across various treatment lines, anthracycline based chemotherapy was used in 36.7% of patients in the 1st line treatment. While, taxane based chemotherapy was used in 38.5% of patients in the 1st line, and 46.7% in the 2nd line. Navelbine, gemcitabine, capcitabine based chemotherapies were mainly seen in the 3rd, 4th and 5th lines. Across various lines, combination chemotherapy was given to the majority of patients. Nonsteroidal aromatase inhibitors (AI) was the main hormonal treatment used in all lines of treatment followed by tamoxifen then steroidal aromatase inhibitors. Only minority of patients were treated by fulvestrant, most of which was seen in third line.
Regarding treatment outcomes, ORR was higher after chemotherapy than ET across various treatment lines. The median PFS after chemotherapy was less than median PFS of hormonal therapy across various treatment lines. The overall toxicity of chemotherapy was significantly higher than the overall toxicity of hormonal therapy. The 1-, 5-, and 10-year survival rates for our patients were 86.2 %, 23.1% and 9% respectively, while the median survival time was 34 months.
Risk factors found to significantly affect PFS in univariate analyses were number of metastatic sites on diagnosis, initial metastatic site and initial type of systemic treatment received. While OS was significantly influenced by Her2 status, number of metastatic sites on diagnosis, the initial metastatic site, total number of lines of systemic treatment and initial type of systemic treatment received. However, age, menopausal status, comorbidities, presentation of metastases either from the start or not and surgery of the primary were not statistically significant predictors of survival. But, on Multivariate analysis OS was significantly influenced by total number of lines of systemic treatment and initial type of systemic treatment received.
In the second part of the study which is physician survey to determine their preferences in choosing treatment of HR positive mBC, the surveyed physicians were in different regions of Egypt, 54.2% of our physicians worked in Alexandria. 20.9% worked in Cairo. 39% of physicians had more than 5 years of practice experience and 39% are consultants of more than 10 years of practice experience. NCCN guidelines were the most frequently consulted guidelines when deciding therapy course. The study was made in the treatment of HR+/Her2- MBC in postmenopausal and premenopausal women, also in