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Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is) are the mainstay of treatment of hormone receptor+/human epidermal growth factor receptor 2-patients with advanced breast cancer (ABC). Despite improvements in overall survival, most patients experience disease progression. Biomarkers derived from a liquid biopsy are appealing for their potential to detect resistance to treatment earlier than computed tomography imaging. However, clinical data concerning microRNAs (miRNAs/miRs) in the context of CDK4/6is are lacking. Thus, the present study assessed the use of miRNAs in patients with ABC treated with CDK4/6is. Patients treated for ABC with CDK4/6is between June and August 2022 were eligible. miRNA expression analyses were performed using a TaqMan™ low-density miRNA array. A total of 80 consecutive patients with ABC treated with CDK4/6is at Maria Sklodowska-Curie National Research Institute of Oncology (Gliwice, Poland) were assessed, with 14 patients diagnosed with progressive disease at the time of sampling, 55 patients exhibited clinical benefit from CDK4/6i treatment and 11 patients were at the beginning of CDK4/6i treatment. Patients with disease progression had significantly higher levels of miR-21 (P=0.027), miR-34a (P=0.011), miR-193b (P=0.032), miR-200a (P=0.027) and miR-200b (P=0.003) compared with patients who benefitted from CDK4/6i treatment. Significantly higher levels of miR-34a expression were observed in patients with progressive disease than in patients beginning treatment (P=0.031). The present study demonstrated the potential innovative role of circulating miRNAs during CDK4/6i treatment. Plasma-based expression of miR-21, −34a, −193b, −200a and −200b effectively distinguished patients with ABC who responded to CDK4/6i treatment from patients who were resistant. However, longitudinal studies are required to verify the predictive and prognostic potential of miRNA. [ABSTRACT FROM AUTHOR]

Palbociclib is a potent cyclin-dependent kinase (CDK)4/6 inhibitor that disrupts cell cycle progression and has been recently approved in combination with an aromatase inhibitor or fulvestrant as first- and second-line treatment in hormone receptor (HR)+, human epidermal growth factor receptor (HER)2- metastatic breast cancer. There is evidence that palbociclib may reverse endocrine therapy resistance and that it may also be added to ongoing endocrine therapy beyond progression to obtain clinical benefit. The aim of the present study was to explore this possibility in 5 patients who received palbociclib + fulvestrant following disease progression while under treatment with fulvestrant alone. The median progression-free survival was not reached during a median follow-up of 25 months, and the most frequent best response was stable disease. Three patients remained under treatment on the last re-evaluation. All patients had highly endocrine-sensitive disease and had previously received fulvestrant for ≥12 months. The hypothesis that a selected subpopulation of patients with HR+/HER2- metastatic breast cancer may benefit from the addition of palbociclib to ongoing endocrine therapy beyond disease progression merits further investigation. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to analyze the clinical and pathological characteristics, treatment, and prognosis of de novo metastatic breast cancer (DnMBC). Information regarding 1,890 patients treated for advanced breast cancer at the Tianjin Medical University Cancer Hospital between January 2008 to December 2017 was collected. Clinicopathological characteristics, treatments and outcomes of these patients were compared using the chi-square test, log-rank test, and Cox regression analysis. A total of 171 patients were diagnosed with DnMBC. The median age at diagnosis was 53 years (range, 23-77). The percentage of T4 staging was higher (37.4%), 69.6% of patients were estrogen receptor (ER) positive, 59.1% were progesterone receptor positive, 29.8% had positive human epidermal growth factor receptor 2 (HER2) status, 68.4% had Ki-67 ≥20%, 55% had oligometastasis at the initial diagnosis, ~87.7% were treated with chemotherapy initially and 24% received palliative surgery for the primary tumor. After a median follow-up time of 26 months, the median progression-free survival (PFS) and overall survival (OS) among patients with DnMBC were 11 (8.7-13.3) months and 34 (27.9-40.1) months, respectively. In the multivariable model, ER status and sites of first metastasis (oligometastasis or polymetastasis) were identified to be independent predictors of PFS (P<0.05); ER status, primary tumor stage, and surgical treatment of primary tumors were identified to be independent predictors of OS (P<0.05). In conclusion, the clinicopathological characteristics of DnMBC are greater invasiveness and a higher risk of progression. Palliative surgical treatment may improve the prognosis of HR+/HER2-patients with oligometastasis. Therefore, individualized treatment as required is particularly important. [ABSTRACT FROM AUTHOR]

GTPase activating proteins (RhoGAPs) serve significant roles in multiple aspects of tumor biology. Genes encoding RhoGAPs (ARHGAP), which switch off Rho-like GTPases, are responsible for breast cancer biogenesis. However, the identification of suitable and novel biomarkers for precision treatment and prognosis remains challenging. The present study aimed to evaluate the expression of ARHGAP family genes in breast cancer and investigate the survival data using the Oncomine, Kaplan-Meier Plotter, bcGenExMiner and cBioPortal online databases. The results demonstrated low expression of ARHGAP6, 7, 10, 14, 19, 23 and 24 and high expression of ARHGAP9, 11, 15, 18 and 30 in patients with breast cancer compared with that in healthy individuals. The survival analysis revealed that low expression levels of ARHGAP6, 7 and 19 were associated with poor relapse-free survival (RFS) and overall survival (OS), whereas high expression levels of ARHGAP9, 15 and 30 were associated with preferable RFS and OS. Metastatic relapse data demonstrated that higher expression of ARHGAP9, 15, 18, 19, 25 and 30 were associated with better prognosis and increased expression of ARHGAP11A and 14 exerted negative effects on patient prognosis. The overlapping genes ARHGAP9, 15, 19 and 30 obtained from these bioinformatics analysis tools exhibited significant association with clinical parameters including age, the presence of estrogen receptor, progesterone receptor and epidermal growth factor receptor-2, Scarff-Bloom-Richardson grade and Nottingham prognostic index. In conclusion, bioinformatics analysis revealed that ARHGAP9, 15, 19 and 30, but not other ARHGAP family genes may be promising targets with prognostic value and biological function for precision treatment of breast cancer. [ABSTRACT FROM AUTHOR]

Population-based study for predicting the prognosis for breast cancer liver metastasis (BCLM) is lacking at present. Therefore, the present study aimed to evaluate newly diagnosed BCLM patients of different tumor subtypes and assess potential prognostic factors for predicting the survival for BCLM patients. Specifically, data were collected from the Surveillance, Epidemiology and End Results program from 2010 to 2014, and were assessed, including the data of patients with BCLM. Differences in the overall survival (OS) among patients was compared via Kaplan-Meier analysis. Other prognostic factors of OS were determined using the Cox proportional hazard model. In addition, the breast cancer-specific mortality was assessed using the Fine and Gray's competing risk model. A nomogram was also constructed on the basis of the Cox model for predicting the prognosis of BCLM cases. A total of 2,098 cases that had a median OS of 20.0 months were included. The distribution of tumor subtypes was as follows: 42.2% with human epidermal growth factor receptor 2 (Her2; -)/hormone receptor (HR; +), 12.8% with Her2(+)/HR(−), 19.1% with Her2(+)/HR(+) and 13.5% with triple negative breast cancer (TNBC). Kaplan-Meier analysis revealed that older age (>64 years), unmarried status, larger tumor, higher grade, no surgery, metastases at other sites, and TNBC subtype were associated with shorter OS. Additionally, multivariate analysis revealed that older age (>64 years), unmarried status, no surgery, bone metastasis, brain metastasis and TNBC subtype were significantly associated with worse prognosis. Thus, age at diagnosis, marital status, surgery, bone metastasis, brain metastasis and tumor subtype were confirmed as independent prognosis factors from a competing risk model. We also constructed a nomogram, which had the concordance index of internal validation of 0.685 (0.650–0.720). This paper had carried out the population-based prognosis prediction for BCLM cases. The survival of BCLM differed depending on the tumor subtype. More independent prognosis factors were age at the time of diagnosis, surgery, marital status, bone metastasis, as well as brain metastasis, in addition to tumor subtype. Notably, the as-constructed nomogram might serve as an efficient approach to predict the prognosis for individual patients. [ABSTRACT FROM AUTHOR]

The most common sites of metastasis for breast cancer are the soft tissues, bones, lungs, liver and brain; however, metastases to the gastrointestinal tract and thyroid gland from breast cancer rarely occur. The present study describes the case of a 30-year-old woman who developed gastric and thyroid metastases 5 years after her initial diagnosis of invasive ductal breast carcinoma. The initial pathological diagnosis when receiving modified radical mastectomy was invasive ductal carcinoma, and further immunohistochemical examination revealed the cancer to be estrogen receptor (−), progesterone receptor (−), human epidermal growth factor receptor 2 (HER2; ++) and Ki-67 (70%). Genetic testing indicated the HER2 amplification mutation, whereas BRCA1/2 testing was negative. A total of 21 months after surgery, during regular follow-up, the patient was revealed to have developed an enlarged lymph node in the left side of the neck and the first recurrence was confirmed. Approximately 5 years after surgery, the patient gradually developed multi-site metastasis, and developed metastases to the thyroid gland and stomach confirmed by pathology and imaging. Combined chemotherapy and targeted therapy were administered and exhibited good efficacy; however, the patient subsequently died due to heart failure. This case report describes the occurrence of gastric and thyroid metastases from breast cancer, and highlights the importance of distinguishing between metastatic and primary tumors. Distinguishing between a metastatic and primary tumor is crucial as treatment protocols vary significantly for these two types of tumors. For patients with a history of breast cancer it should first be considered whether they have metastasis of the primary disease or discomfort caused by treatment; however, the possibility of a second primary tumor cannot be ignored. If the patient has symptoms such as loss of appetite, nausea, vomiting, stomach pain and stomach discomfort, a gastroscopy should be performed in a timely manner. [ABSTRACT FROM AUTHOR]

Matrix metalloproteinase 1 (MMP-1) is a member of the zinc-dependent endopeptidase family, which cleaves the extracellular matrix. The present study investigated the functional role of MMP-1 in breast cancer ex vivo and in vitro in order to determine the underlying molecular mechanisms. The levels of MMP-1 were analyzed in 99 breast cancer specimens using immunohistochemistry and western blotting. A stable short hairpin RNA (shRNA) knockdown of MMP-1 expression was performed in MCF-7 and MDA-MB-231 breast cancer cells, and the effects were examined using MTT and colony formation assays, as well as migration and invasion assays, while western blotting was used to detect the activation of intracellular signaling. The MMP-1 protein was more highly expressed in triple-negative breast cancer tissues than in estrogen receptor(+) and human epidermal growth factor 2 receptor(3+) breast cancer tissues (P<0.05). Furthermore, the MMP-1 levels were significantly higher in the tumor and tumor stromal cells of lymph node metastatic breast cancer tissues than in those of non-metastatic tissues. The knockdown of MMP-1 expression in MCF-7 and MDA-MB-231 cells using MMP-1 shRNA significantly inhibited cell proliferation, migration and invasion, and the expression of the Myc proto-oncogene protein, phosphorylated and total RAC-α serine/threonine-protein kinase 1, and B-cell lymphoma 2, but increased the protein levels of apoptosis regulator BAX and caspase 3. In conclusion, the data suggest that MMP-1 serves an important role in breast cancer development and metastasis. Future studies should assess MMP-1 as a prognostic marker for patients with breast cancer and its inhibition as a novel strategy for controlling breast cancer. [ABSTRACT FROM AUTHOR]

Trastuzumab and pertuzumab with taxane-based chemotherapy are considered the first-line standard therapy for human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (mBC). Pertuzumab is also a later-line therapy for mBC in Switzerland, although limited safety and efficacy data are available. The present study assessed the therapeutic regimens, toxicities and clinical outcomes after second- or later-line pertuzumab therapy in patients with mBC who did not receive pertuzumab as a first-line therapy. Physicians from nine major Swiss oncology centers retrospectively completed a questionnaire for each pertuzumab-naive patient who was treated with pertuzumab as a second- or later-line therapy. Of 35 patients with HER2-positive mBC (median age, 49 years; range, 35-87 years), 14 received pertuzumab as a second-line therapy, 6 as a third-line therapy, and 15 as a fourth- or later-line therapy. A total of 20 patients (57%) died during the study period. The median overall survival was 74.2 months (95% confidence interval, 47.6-139.8 months). Grade (G) 3/4 adverse events (AEs) were reported in 14% of patients, with only 1 patient discontinuing therapy due to pertuzumab-related toxicities. The most common AE was fatigue (overall, 46%; G3, 11%). Overall, congestive heart disease occurred in 14% of patients (G3, 6%), nausea in 14% of patients (all G1), and myelosuppression in 12% of patients (G3, 6%). In conclusion, the median overall survival of patients who underwent second- or later-line pertuzumab treatment was similar to that reported for patients who underwent first-line pertuzumab treatment, and the safety profile was acceptable. These data support the use of pertuzumab for second- or later-line therapy when it was not administered as first-line therapy. [ABSTRACT FROM AUTHOR]

For prognostic assessment in women who receive radiotherapy (RT) for bone metastases (BMs) from breast cancer (BC), prognostic factors specific for BMs from BC were investigated in the present study. The prognostic assessment was performed by retrospectively reviewing 143 women who received first-time RT for BMs from BC between January 2007 and June 2018. The median follow-up time and median overall survival (OS) time from the first-time RT for BMs were 22 and 18 months, respectively. In the multivariate analysis, nuclear grade 3 (NG 3) [hazard ratio, 2.18; 95% confidence interval (CI), 1.34-3.53], brain metastases (hazard ratio, 1.96; 95% CI, 1.01-3.81), liver metastases (hazard ratio, 1.75; 95% CI, 1.17-2.63), performance status (PS) (hazard ratio, 1.63; 95% CI, 1.10-2.41) and previous systemic therapy (hazard ratio, 1.58; 95% CI, 1.03-2.42) were significant factors for OS, whereas age, hormone-receptor/human epidermal growth factor receptor 2 status, number of BMs and synchronous lung metastases were not significant factors. When points according to risk levels [unfavorable points (UFPs)] were assigned to each risk factor (1.5 points for NG 3 and brain metastases; and 1 point for PS ≥2, previous systemic therapy and liver metastases), the median OS times of patients with a total number of UFPs ≤1 (n=45), 1.5–3 (n=55) and ≥3.5 (n=43) were 36, 17 and 6 months, respectively. Overall, in patients who received first-time RT for BMs from BC, NG 3, brain/liver metastases, poor PS and previous systemic therapy were unfavorable prognostic factors. Comprehensive prognostic assessment using these factors seemed to be useful for the prediction of prognoses in patients with BMs from BC. [ABSTRACT FROM AUTHOR]

Although human epidermal growth factor receptor 2 (HER2)-targeted therapy significantly improves the prognosis of patients with HER2-positive breast cancer, most patients with advanced breast cancer eventually progress due to drug resistance. At present, there is no standard treatment after patients become resistant to HER2-targeted therapy. Previous studies have indicated that anti-angiogenesis drugs have potential efficacy in the treatment of advanced breast cancer. The present study reported on a case of a pretreated patient with HER2-positive advanced breast cancer with brain metastases who developed resistance to multiple lines of HER2-targeted treatment. The patient was treated with apatinib combined with trastuzumab and albumin-bound paclitaxel. The patient achieved partial response to the third-line treatment with a progression-free survival of 9 months. After combination treatment, the symptoms of headache and vomiting were relieved and all the brain metastases were significantly reduced. The present case indicated that apatinib may have anti-tumor activity in patients with HER2-positive breast cancer with HER2-targeted drug resistance. The present case provides valuable information and may offer a new possibility for the treatment of patients with breast cancer with brain metastases who progressed after clinical treatment with small-molecule anti-HER2 tyrosine kinase inhibitor drugs. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) with overexpression of human epidermal growth factor receptor 2 (HER2) is closely associated with an elevated risk of multiple distant metastases and unfavorable prognosis. Disitamab Vedotin (RC48) is a newly developed antibody-drug conjugate targeting HER2, which is comprised of hertuzumab coupled to monomethyl auristatin E via a cleavable linker. Pre-clinical studies indicated its strong anti-tumor activity in HER2-positive and low HER2 expression models of BC. The present study reported on the case of a 60-year-old postmenopausal female who suffered from fatigue and was diagnosed with a right-sided BC tumor. The diagnosis was stage IV (cT4N3M1) hormone receptor (HR)-positive and HER2-positive invasive ductal carcinoma with systemic metastases (brain included). The patient initially responded well to 26 cycles of the first-line anti-HER2 targeted therapy plus chemotherapy (trastuzumab+pertuzumab+nab-paclitaxel) combined with whole-brain radiotherapy. However, both extracranial and intracranial lesions achieved progressive disease (PD), which eventually occurred during 5 sequential cycles of maintenance therapy. Subsequently, 4 cycles of second-line treatment (trastuzumab + pyrotinib + capecitabin) were continued until the levels of blood tumor markers CEA, CA15-3 and CA125 were elevated, and systemic PD was able to be attained (the brain metastases were rated as stable disease). Finally, the patient received RC48 as the third-line therapy and achieved a durable and effective clinical response. To date, the patient has benefited from 12 cycles of RC48 without any severe adverse effects. The overall survival was >3 years. The present study showcased that RC48 was effective and tolerable for a patient with HR- and HER2-positive BMBC. [ABSTRACT FROM AUTHOR]

The addition of palbociclib (a cyclin-dependent kinase 4/6 inhibitor) to endocrine therapy (ET) has been shown to significantly improve progression-free survival (PFS) and overall survival (OS) among patients with hormone receptor-positive (HR+) advanced breast cancer. The current study presents the local experience of using palbociclib at two cancer centers in Saudi Arabia. Electronic data of patients with metastatic HR+ and human epidermal growth factor receptor 2-negative breast cancer who progressed after prior ET and received at least one cycle of palbociclib plus ET, were retrospectively reviewed. A total of 97 patients were identified, and their data were included in the analysis. The median age of the patients was 55 years. Patients were heavily pretreated in the metastatic setting (55% received systemic chemotherapy and 49% received two or more lines of prior ET). In total, 29 (30%) and 50 (52%) patients achieved an objective response and clinical benefit, respectively. The median follow-up time was 31.0 months [95% confidence interval (CI), 16.9-44.9] and the median PFS time was 16.3 months (95% CI, 11.4-21.2), with 58% of patients remaining progression-free at 12 months. Upon multivariate regression analysis, liver involvement was the only significant independent variable that predicted a greater risk of progression or death (hazard ratio, 2.32; 95% CI, 1.22-4.40; P=0.010). The median OS time was 19.6 months (95% CI, 18.1-20.9), with 12- and 24-month OS rates of 75 and 30%, respectively. Overall, real-world data showed that administration of palbociclib in combination with ET in patients with advanced HR+ breast cancer achieved a favorable outcome that was comparable to that reported in clinical trials. [ABSTRACT FROM AUTHOR]

Cyclin-dependent-kinase 4–6 inhibitors (CDK4/6i) have improved the management of hormone receptor (HR)+/human epidermal growth factor receptor (HER)2− metastatic breast cancer (mBC). Currently, there are no valid prognostic factors for response to CDK4/6i. Baseline lymphopenia is reported as a prognostic factor in several types of cancer. The present retrospective study aimed to evaluate the effect of baseline absolute lymphocyte count (ALC) on response to palbociclib. Progression-free survival (PFS) was the primary endpoint. Secondary endpoints were overall survival (OS), best response and safety. A total of 114 patients treated for mBC between 2016 and 2019 were included. Median baseline ALC was 1.4 g/l (range, 0.2-4.3 g/l). A total of 65 (57%) and 49 (43%) patients had baseline ALC values of <1.5 and ≥1.5 g/l, respectively. Patients with baseline lymphopenia exhibited significantly shorter PFS (6 vs. 10 months; P=0.004) and OS (20 vs. 33 months; P=0.02). ALC <1.5 g/l independently predicted worse survival, as indicated by multivariate analysis (P=0.04; hazard ratio, 1.76; 95% confidence interval, 1.02-3.02). Patients with baseline ALC <1.5 g/l had significantly less partial response (14 vs. 22%; P=0.016) and more disease progression (46 vs. 20%; P=0.016) than those with ALC ≥1.5 g/l. ALC is a strong and easy-to-use dosage with prognostic factor for patients with HR+/HER2− mBC treated with palbociclib and endocrine therapy. Lymphopenia may also be a predictive factor of early progression. These data need to be verified in a larger prospective study. [ABSTRACT FROM AUTHOR]

The purpose of the current study was to investigate the hypothesis that the spatial distribution of brain metastases could be affected by the biological subtypes of breast cancer. CT (n=1) or MRI (n=66) images of 67 patients with a total of 437 treatment-naive brain metastases from breast cancer were retrospectively reviewed. Patients were grouped according to the biological subtype of the tumor [luminal A, 28; luminal B, 9; human epidermal growth factor receptor 2 (HER2) positive, 14; triple-negative breast cancer (TNBC), 16]. All images were standardized to the human brain MRI atlas provided by the Montreal Neurological Institute 152 database. The distribution pattern of brain metastases after image standardization was analyzed. The cerebellum and the frontal lobe were more commonly affected by breast cancer brain metastases. Brain metastases from luminal A and B types of breast cancer arose more often in the cerebellum. Brain metastases from HER2-positive type breast cancer occurred more often in the putamen and the thalamus and less frequently in the cerebellum than other types (P=0.0057). The subtypes of breast cancer are related to differences in the spatial distributions of their brain metastases. These differences may be utilized to plan different cranial irradiation strategies according to the breast cancer subtypes. [ABSTRACT FROM AUTHOR]

Checkpoint with FHA and RING finger domains (CHFR) is a G2 phase/mitosis checkpoint. Several studies have reported that CHFR is downregulated in multiple cancer types and serves a tumor suppressor role. However, the biological function of CHFR in breast cancer (BRCA), particularly regarding metastasis, are yet to be elucidated. In the present study, it was revealed that CHFR is upregulated in BRCA compared with normal tissues, according to The Cancer Genome Atlas database. In addition, subgroup analysis of BRCA revealed that CHFR was upregulated in both human epidermal growth factor receptor 2-positive and triple-negative BRCA. Meanwhile, patients with high expression levels of CHFR exhibited poorer overall survival rates. Furthermore, the present data revealed that the overexpression of CHFR in SKBR3 cells resulted in enhanced cell migration and invasiveness, and also significantly upregulated mesenchymal markers, such as N-cadherin, vimentin, transcription factor Slug and tight junction protein claudin-1. Furthermore, knockdown of CHFR in MDA-MB-231 cells significantly inhibited cell migration and invasiveness, and also downregulated mesenchymal markers, such as N-cadherin, vimentin and tight junction protein claudin-1. In conclusion, the current results indicated that CHFR expression was associated with cell metastasis in BRCA by mediating epithelial-to-mesenchymal transition. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer has been historically associated with an aggressive disease course with common distant metastasis and poor prognosis. HER2-targeting therapies have significantly changed treatment and drastically improved outcomes for this group of patients. However, primary or acquired resistance to anti-HER2 regimens leads almost universally to disease progression, often with difficult to treat central nervous system (CNS) metastases. The current review summarized the existing therapeutic options for HER2-positive metastatic disease in the first, second and further line setting. Furthermore, novel agents currently under development were presented, which have demonstrated encouraging results in heavily pretreated patients or specific subgroups, such as HR-positive/HER2-positive tumors and CNS disease. [ABSTRACT FROM AUTHOR]

Bone is the most common site of metastatic spread in patients with breast cancer. Patients with bone-only metastasis (BOM) are a unique group. The aim of the present study was to compare the clinicopathological characteristics, survival and prognostic factors of patients with BOM and non-BOM. The clinical data of 1,290 patients with metastatic breast cancer treated at the Tianjin Medical University Cancer Institute and Hospital (Tianjin, China) between January 2008 and December 2017 were reviewed. The clinical data were divided into a BOM group (n=208 cases) and a non-BOM group (n=1,082 cases). Patients with BOM had longer disease-free survival, progression-free survival (PFS) and overall survival (OS) compared with patients in the non-BOM group. The hormone receptor (HR) status and number of metastases were significant influencing factors of PFS in the BOM group. Furthermore, the HR status, location of bone metastasis and number of bone metastases were significantly associated with OS of patients in the BOM group. Age at diagnosis of metastasis, HR status and tumor stage were significantly associated with OS in the non-BOM group. In the BOM group, patients with HR+/human epidermal growth factor receptor 2 (HER2)− tumors had the most favorable prognosis. In the non-BOM group, patients with HR+/HER2− and HER2+ tumors had improved prognosis. In the BOM with HR+/HER2− subgroup, the PFS and OS of patients receiving endocrine therapy or sequential therapy (chemotherapy followed by endocrine therapy) was significantly improved compared with those receiving chemotherapy alone (P<0.05). Skeletal-related events were significantly associated with the number of bone metastases (P<0.001). The most common secondary metastatic site in the BOM group was the liver. The prognosis of the patients in the BOM group was improved compared with that in the non-BOM patients. HR− and multiple bone metastases, as well as combined axial and appendicular bone metastases, were significantly associated with poor prognosis in the patients with BOM. For patients in the HR+/HER2− BOM subgroup, endocrine therapy alone resulted in satisfactory results. [ABSTRACT FROM AUTHOR]

Breast cancer is a highly heterogeneous disease at the molecular level and >90% of mortalities are due to metastasis and its associated complications. The present study determined the impact of molecular subtypes on metastatic behavior and overall survival (OS) of patients with metastatic breast cancer. The influence of molecular subtypes on the sites and number of metastases in 166 patients with metastatic breast cancer from a single center were assessed; and the influence of molecular subtypes on the sites and number of metastases and OS in 15,322 metastatic cases among 329,770 patients with primary breast cancer from the Surveillance, Epidemiology and End Results database were assessed. Analysis of both datasets revealed that different molecular subtypes exhibited differences in the prevalence of different metastatic sites and number of metastases. A larger proportion of bone metastasis was observed in the hormone receptor (HR)+/human epidermal growth factor receptor 2 (HER2)+ subtype than in other subtypes, more lung metastasis was observed in the HR-/HER2+ subtype and more liver metastasis occurred in the HR+/HER2+ and HR-/HER2+ subtypes. Single-site metastasis was more common for the HR+/HER2− subtype than in other subtypes, while 2–3 sites of metastases were more common for the HR+/HER2+ subtype and ≥4 sites of metastases were more frequent in the HR-/HER2+ and HR-/HER2- subtypes. The mean OS of patients with primary breast cancer in the HR+/HER2− subtype group was the longest (78.5 months), while the HR-/HER2- group had the shortest mean OS (69.1 months). The mean OS of the metastatic HR+/HER2+ group was the longest (46.0 months), while the mean OS of the metastatic HR-/HER2- group was the shortest (18.5 months). In conclusion, the results of the present study suggested that different molecular subtypes of breast cancer have different metastatic behavior, as well as mean OS. [ABSTRACT FROM AUTHOR]