Breast cancer is the most common type of cancer and the leading cause of cancer-related deaths in women in Turkey. This study presents the characteristics of patients registered in National Breast ...Cancer Registry Program of Turkish Federation of Breast Diseases Societies.
The registry contains 242 variables under 10 categories and 699 questions. Patients were recorded (online and offline) from nationwide breast centers around Turkey.
Twenty-thousand patients were registered between May 2005 and April 2017 at 36 centers. After data cleaning, 19,503 women were included in the study. The median age at diagnosis was 51 14-97; 17.2% were younger than 40 and 37.2% were premenopausal; 13.6% were nulliparous. Breast conserving surgery rate was 39.3%. Histopathology was invasive ductal cancer in 77%. Majority of patients had stage II cancer (48.3%). Estrogen, progesterone and HER-2 receptor positivity rates in invasive breast cancer were 72.5%, 62.5% and 21.8%, respectively. The mean tumor diameter was 2.5±1.7 cm. During the mean 51.6 months of follow-up, the local/regional and systemic recurrence rates were 3.7% and 5.2%, respectively; five and 10-year overall survival rates were 86% and 76%.
Despite increasing number of screening centers and free-of-charge mammography (ages 40 to 69) and mobile screening systems in recent years, a significant portion of patients were diagnosed at advanced stage due to lack of breast cancer awareness. In contrast with the study published 5 years ago, there was a decrease in the rate of pre-menopausal women and an increase in the breast conserving surgery.
Adjuvant radiotherapy (RT) after breast-conserving surgery (BCS) for ductal carcinoma in situ (DCIS) is debated as benefits are inconstant. Molecular signatures for DCIS have been developed to ...stratify the risk of local recurrence (LR) and therefore guide the decision of RT.
To evaluate, in women with DCIS treated by BCS, the impact of adjuvant RT on LR according to the molecular signature risk stratification.
We conducted a systematic review and meta-analysis of five articles including women with DCIS treated by BCS and with a molecular assay performed to stratify the risk, comparing the effect of BCS and RT versus BCS alone on LR including ipsilateral invasive (InvBE) and total breast events (TotBE).
The meta-analysis included 3478 women and evaluated two molecular signatures: Oncotype Dx DCIS (prognostic of LR), and DCISionRT (prognostic of LR and predictive of RT benefit). For DCISionRT, in the high-risk group, the pooled hazard ratio of BCS + RT versus BCS was 0.39 (95%CI 0.20-0.77) for InvBE and 0.34 (95%CI 0.22-0.52) for TotBE. In the low-risk group, the pooled hazard ratio of BCS + RT versus BCS was significant for TotBE at 0.62 (95%CI 0.39-0.99); however, it was not significant for InvBE (HR = 0.58 (95%CI 0.25-1.32)), Discussion: Molecular signatures are able to discriminate high- and low-risk women, high-risk ones having a significant benefit of RT in the reduction of invasive and in situ local recurrences, while in low-risk ones RT did not have a benefit for preventing invasive breast recurrence. The risk prediction of molecular signatures is independent of other risk stratification tools developed in DCIS, and have a tendency toward RT de-escalation. Further studies are needed to assess the impact on mortality.
Estradiol (E2), a follicle-stimulating hormone (FSH), AMH, and inhibin B levels, along with AFC and MOV, are used to determine ovarian reserve in pre-menopausal women. Studies have shown that AMH ...levels are more sensitive than those of E2, FSH, and inhibin B and that AFC and MOV can be used to evaluate ovarian reserve. AMH, AFC, and MOV measurements were performed before and after adjuvant SC in 3-month periods for one year. Patients were classified as experiencing chemotherapy-induced amenorrhea (CIA) if they did not have menstrual cycles for a period of six months or longer following the conclusion of their chemotherapy treatment. We aimed to evaluate the factors affecting chemotherapy-induced amenorrhea in breast cancer patients treated with adjuvant chemotherapy and the performance of baseline measurements of AMH, AFC, and MOV to predict chemotherapy-induced amenorrhea. The effects of different chemotherapy regimens on the AMH level, AFC, and MOV in CIA patients were investigated. Seventy-one patients were eligible for this study, and the median age was 38 years (range: 23–45). The median follow-up was 37 months (range: 20–51), and CIA developed in 62% of the patients. The AMH level and AFC were significantly decreased one year after SC (p < 0.0001), whereas MOV was not (p = 0.507). AMH levels before chemotherapy (median: 1.520 vs. 0.755, p = 0.001) and at the end of the first year (median: 0.073 vs. 0.010, p = 0.030) and pre-treatment AFC (median: 12 vs. 4.50, p = 0.026) were lower in patients with CIA compared to those without CIA. The AMH levels before SC were the most valuable and earliest factor for predicting CIA development. In addition, there was no difference between the chemotherapy regimens (including or not including taxane) in terms of CIA development.
The Oncotype Dx recurrence score (ODx-RS) guides the adjuvant chemotherapy decision-making process for patients with early-stage hormone receptor-positive, HER-2 receptor-negative breast cancer. This ...study aimed to evaluate survival and its correlation with ODx-RS in pT1-2, N0-N1mic patients treated with adjuvant therapy based on tumor board decisions.
Estrogen-positive HER-2 negative early-stage breast cancer patients (pT1-2 N0, N1mic) with known ODx-RS, operated on between 2010 and 2014, were included in this study. The primary aim was to evaluate 5-year disease-free survival (DFS) rates according to ODX-RS.
A total of 203 eligible patients were included in the study, with a median age of 48 (range 26-75) and median follow-up of 84 (range 23-138) months. ROC curve analysis for all patients revealed a recurrence cut-off age of 45 years, prompting evaluation by grouping patients as ≤45 years vs. >45 years. No significant difference in five-year DFS rates was observed between the endocrine-only (ET) and chemo-endocrine (CE) groups. However, among the ET group, DFS was higher in patients over 45 years compared to those aged ≤45 years. When stratifying by ODx-RS as 0-17 and ≥18, DFS was significantly higher in the former group within the ET group. However, such differences were not seen in the CE group. In the ET group, an ODx-RS ≥18 and menopausal status were identified as independent factors affecting survival, with only an ODx-RS ≥18 impacting DFS in patients aged ≤45 years. The ROC curve analysis for this subgroup found the ODx-RS cut-off to be 18.
This first multicenter Oncotype Dx survival analysis in Turkey demonstrates the importance of Oncotype Dx recurrence score and age in determining treatment strategies for early-stage breast cancer patients. As a different aproach to the literature, our findings suggest that the addition of chemotherapy to endocrine therapy in young patients (≤45 years) with Oncotype Dx recurrence scores of ≥18 improves DFS.
ObjectiveTherapeutic management of ductal carcinoma in situ (DCIS) is heterogeneous among countries worldwide, and some treatment indications are still controversial. To investigate DCIS management ...in different countries; identify both consensual practices and controversial topics; and survey opinions about the future management of DCIS. Materials and MethodsThe Senologic International Society network members participated to an online survey using a questionnaire, between November 2021 and February 2022. ResultsTwenty-two responses from 20 different countries showed that organized breast cancer screening programs were present for 87% participants, and DCIS cases represented 13.7% of all breast cancers. Most participants used the grade classification (100%), the morphological classification (78%) and performed immunohistochemistry assays (73%). In case of conservative treatment, the mean re-excision rate was 10.3% and clear margins of mean 2.5 mm were considered healthy. Radical mastectomy rate was 35.5% with a breast reconstruction rate of 53%. Tumor bed boost indications were heterogeneous, and 73% of participants indicated hormone therapy for hormone-positive DCIS. Surgery and radiotherapy omission for some low-risk DCIS were considered by 73% of participants. Multigene assays were used by 43% of participants. Concerning future changes in DCIS management, participants mostly answered surgical de-escalation (48%), radiotherapy de-escalation (35) and/or active surveillance for some cases (22%). ConclusionThis survey provided an overview of the current practices of DCIS management worldwide. It showed that some areas are rather consensual: incidence increases over time, treatment in young women, pathological classifications, definition of healthy margins, the skin-sparing mastectomy and immediate breast reconstruction. However, some topics are still debated and result in heterogeneous practices, such as evolution in the age of diagnosis, the benefit of de-escalation in low-risk DCIS among elderly women, indications for hormone therapy, radiotherapy omission, or multigene assays. Further evidence is needed to reach consensus on these points, and innovative approaches are still under evaluation in clinical trials. The International Senologic Society, by its members, encourages precision medicine and personalized treatments for DCIS, to avoid overtreatment and overdiagnosis, and provide better healthcare to women with DCIS.
Mammographic screening and management of breast cancer (BC) in elderly women are controversial and continue to be an important health problem. To investigate, through members of the Senologic ...International Society (SIS), the current global practices in BC in elderly women, highlighting topics of debate and suggesting perspectives.
The questionnaire was sent to the SIS network and included 55 questions on definitions of an elderly woman, BC epidemiology, screening, clinical and pathological characteristics, therapeutic management in elderly women, onco-geriatric assessment and perspectives.
Twenty-eight respondents from 21 countries and six continents, representing a population of 2.86 billion, completed and submitted the survey. Most respondents considered women 70 years and older to be elderly. In most countries, BC was often diagnosed at an advanced stage compared to younger women, and age-related mortality was high. For this reason, participants recommended that personalized screening be continued in elderly women with a long life expectancy.In addition, this survey highlighted that geriatric frailty assessment tools and comprehensive geriatric evaluations needed to be used more and should be developed to avoid undertreatment. Similarly, multidisciplinary meetings dedicated to elderly women with BC should be encouraged to avoid under- and over-treatment and to increase their participation in clinical trials.
Due to increased life expectancy, BC in elderly women will become a more important field in public health. Therefore, screening, personalized treatment, and comprehensive geriatric assessment should be the cornerstones of future practice to avoid the current excess of age-related mortality. This survey described, through members of the SIS, a global picture of current international practices in BC in elderly women.
IGFBP5 is an important regulatory protein in breast cancer progression. We tried to identify differentially expressed genes (DEGs) between breast tumor tissues with IGFBP5 overexpression and their ...adjacent normal tissues. In this study, thirty-eight breast cancer and adjacent normal breast tissue samples were used to determine IGFBP5 expression by qPCR. cDNA microarrays were applied to the highest IGFBP5 overexpressed tumor samples compared to their adjacent normal breast tissue. Microarray analysis revealed that a total of 186 genes were differentially expressed in breast cancer compared with normal breast tissues. Of the 186 genes, 169 genes were downregulated and 17 genes were upregulated in the tumor samples. KEGG pathway analyses showed that protein digestion and absorption, focal adhesion, salivary secretion, drug metabolism-cytochrome P450, and phenylalanine metabolism pathways are involved. Among these DEGs, the prominent top two genes (MMP11 and COL1A1) which potentially correlated with IGFBP5 were selected for validation using real time RT-qPCR. Only COL1A1 expression showed a consistent upregulation with IGFBP5 expression and COL1A1 and MMP11 were significantly positively correlated. We concluded that the discovery of coordinately expressed genes related with IGFBP5 might contribute to understanding of the molecular mechanism of the function of IGFBP5 in breast cancer. Further functional studies on DEGs and association with IGFBP5 may identify novel biomarkers for clinical applications in breast cancer.
A better understanding of tumor biology and new drugs have led to significant changes in the management of breast cancer (BC). Radical mastectomy, which had been the treatment for BC for more than a ...century, was based on the hypothesis that BC is a local-regional disease. In the 1970s, Fisher's studies showed that cancer cells could reach the systemic circulation without passage through the regional lymphatic system. Multidisciplinary treatment of BC, which was now considered a systemic disease, was started and radical mastectomy was replaced by breast-conserving surgery (BCS)+, axillary dissection (AD), systemic chemotherapy, hormonotherapy, and radiotherapy in early-stage BC. Modified radical mastectomy, chemotherapy, and radiotherapy were applied as a treatment for locally advanced BC. However, later clinical studies demonstrated that the breast can be preserved in those who respond well to neo-adjuvant chemotherapy (NAC). In the early 1990s, sentinel lymph node biopsy (SLNB) in early-stage BC (cN0) was performed using blue dye and radioisotope markers. It was shown that AD may be avoided in SLN-negative patients, and SLNB has been a standard intervention in cN0 patients. In this way, the very serious complications of AD, especially lymphedema, were avoided. BC has been shown to be a heterogeneous disease and the tumor may be divided into four different molecular subtypes. Thus, optimal treatment differed from patient to patient (one size fits all was inappropriate), individualized treatments have emerged and over-treatment was avoided. The prolongation of life expectancy and the decrease in recurrence led to an increase in the rate of BCS, an acceptable cosmetic result with oncoplastic surgery, and a better quality of life. The increase in the rate of complete response to NAC with new and targeted agents and especially in human epidermal growth factor receptor-2+ and triple-negative patients with a poor prognosis has led to the use of NAC regardless of cN0. The complete disappearance of the tumor after NAC has been reported by some studies, suggesting that breast surgery may not be needed. However, other studies have shown that vacuum biopsies performed on the tumor bed have a high rate of false negativity. Therefore, it is difficult to suggest that there is no need for lumpectomy, which is cheaper and safer today. The false negativity rate of SLNB is high in patients with cN1 at the time of diagnosis and cN0 after NAC (approximately 13%). In order to reduce this rate to ≤5%, clinical studies have recommended the use of the dual method, marking the positive lymph node before chemotherapy and removing 3-4 nodules with SLN. In summary, a better understanding of tumor biology and new drugs have changed the management of BC and de-escalate the role of surgical treatment.
The association of breast cancer and thyroid autoimmunity has been suggested by many studies in the literature, but the causality still needed to be proven. With this study we aimed to search the ...correlation between thyroid autoimmunity and breast cancer prognostic factors.
To this prospective cohort study 200 consecutive breast cancer patients, who were operated in our clinic were included. Patients' serum thyroid hormone, anti-thyroglobuline (anti-TG) and anti-thyroid peroxidase (anti-TPO) levels and tumors' prognostic parameters (tumor size, axillary involvement, histological grade, lymphovascular invasion, receptor status, Ki-67 proliferation index) were collected. The correlation between serum thyroid autoantibody levels and tumor's prognostic factors were studied.
The prevalence of thyroid autoimmunity (high levels of serum anti-TPO and/or anti-TG) was 18.5% (n=37). Patients with thyroid autoimmunity had a significant lower rate of axillary involvement and a lower rate of Ki-67 proliferation index (22% vs. 46% p=0,007 and 12.73% vs. 20.72% p=0.025, respectively) and were more commonly included to the "low-risk" group (<14%) according to their Ki-67 scores (68% vs. 46%; p=0.015). Other parameters did not differ between the two groups.
We found a favorable correlation between thyroid autoimmunity and axillary involvement and also Ki-67 proliferation index score, which are two crucial and strongly predictive parameters of breast cancer prognoses. This supports the idea of thyroid autoimmunity being a favorable prognostic parameter. Further studies are necessary to investigate the reasons of protective or predictive effect of high thyroid peroxidase levels in breast cancer patients.
ObjectiveThis study aimed to evaluate the relationship between PREDICT tool overall survival (OS) scores and high-risk patients according to TAILORx risk categorization in elderly hormone reseptor ...(HR) positive human epidermal growth factor negative early breast-cancer patients. Materials and MethodsWe conducted a retrospective study, extracting data from medical records of 64 patients diagnosed with breast cancer. A retrospective analysis was performed on all patients who had Oncotype Dx Recurrence Scores across five medical centers between 2017 and 2022. PREDICT scores were defined as calculated 10-year OS rates via PREDICT tool. ResultsThe median age of the patients was 67, with a range between 65-75 years. Low-risk patients had a slightly higher two PREDICT scores compared to high-risk patients (78% vs. 73%), (81% vs. 77%), which were statistically significant. The progesterone receptor (PR) level was significantly lower in the high-risk group (3.5% vs. 80%). A unit decrease in the PREDICT scores was associated with a 11% increase in the odds of being in the high-risk group. However, these effects weren't statistically significant in the multivariate analysis. A unit decrease in the PR level was significantly associated with increased odds (by 5% in the multivariate analysis) of being in the high-risk group. ConclusionOur study underscores the importance of using a combination of tools, including the PREDICT tool, PR levels, and TAILORx risk categorization, for a comprehensive risk assessment in these patients, especially in the older population. Accurate risk assessment is crucial for tailoring the treatment and optimizing outcomes in this vulnerable population. Future studies are warranted to further validate these findings in larger cohorts and to explore additional biomarkers and genomic signatures that may aid in the risk assessment and management of breast cancer in older patients.
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