Genomic Alterations of Tumors in HER2-Low Breast Cancers.

The aim of this study was to elucidate molecular profiling in HER2-low tumors based on a promising dataset. A total of 615 consecutive HER2-negative breast cancer samples were assayed. The genomic mutations in the two groups with different HER2 expression levels (HER2-0 vs. HER2-low) were compared. The mutation types obtained via next-generation targeted sequencing were correlated with the clinicopathological features of the patients with HER2-0 and HER2-low breast cancer. The results showed that there was a significantly higher percentage of receptor-positive (ER/PR) tumors and more low-level Ki-67 tumors, but a lower incidence of stage I/II tumors in the HER2-low group compared to the HER2-0 group. There was a significantly higher frequency of 17.62% (65/369) for PIK3CA_SNA in the HER2-low group than in the HER2-0 group, which had a frequency of only 9.35% (23/246) (p = 0.006). When the called gene alterations in the triple-negative breast cancer (TNBC) group were compared with those in the luminal-like breast cancer group, there was a significantly high frequency of 28.17% (140/497) for ERBB2_SNA in a luminal-like group than in the TNBC group(16.95% (20/118)).We conclude that the early detection of PIK3CA mutations is likely to be important and might help therapeutic decision making in patients with HER2-low tumors.

Prevalence of BRCA1, BRCA2, and PALB2 genomic alterations among 924 Taiwanese breast cancer assays with tumor-only targeted sequencing: extended data analysis from the VGH-TAYLOR study.

BACKGROUND: The homologous recombination (HR) repair pathway for DNA damage, particularly the BRCA1 and BRCA2 genes, has become a target for cancer therapy, with poly ADP-ribose polymerase (PARP) inhibitors showing significant outcomes in treating germline BRCA1/2 (gBRCA1/2) mutated breast cancer. Recent studies suggest that some patients with somatic BRCA1/2 (sBRCA1/2) mutation or mutations in HR-related genes other than BRCA1/2 may benefit from PARP inhibitors as well, particularly those with PALB2 mutations. The current analysis aims to evaluate the prevalence of genetic alterations specific to BRCA1, BRCA2, and PALB2 in a large cohort of Taiwanese breast cancer patients through tumor-targeted sequencing. METHODS: A total of 924 consecutive assays from 879 Taiwanese breast cancer patients underwent tumor-targeted sequencing (Thermo Fisher Oncomine Comprehensive Assay v3). We evaluated BRCA1, BRCA2, and PALB2 mutational profiles, with variants annotated and curated by the ClinVAR, the Oncomine™ Knowledgebase Reporter, and the OncoKB™. We also conducted reflex germline testing using either whole exome sequencing (WES) or whole genome sequencing (WGS), which is ongoing. RESULTS: Among the 879 patients analyzed (924 assays), 130 had positive mutations in BRCA1 (3.1%), BRCA2 (8.6%), and PALB2 (5.2%), with a total of 14.8% having genetic alterations. Co-occurrence was noted between BRCA1/BRCA2, BRCA1/PALB2, and BRCA2/PALB2 mutations. In BRCA1-mutated samples, only p.K654fs was observed in three patients, while other variants were observed no more than twice. For BRCA2, p.N372H was the most common (26 patients), followed by p.S2186fs, p.V2466A, and p.X159_splice (5 times each). For PALB2, p.I887fs was the most common mutation (30 patients). This study identified 176 amino acid changes; 60.2% (106) were not documented in either ClinVAR or the Oncomine™ Knowledgebase Reporter. Using the OncoKB™ for annotation, 171 (97.2%) were found to have clinical implications. For the result of reflex germline testing, three variants (BRCA1 c.1969_1970del, BRCA1 c.3629_3630del, BRCA2 c.8755-1G > C) were annotated as Pathogenic/Likely pathogenic (P/LP) variants by ClinVar and as likely loss-of-function or likely oncogenic by OncoKB; while one variant (PALB2 c.448C > T) was not found in ClinVar but was annotated as likely loss-of-function or likely oncogenic by OncoKB. CONCLUSION: Our study depicted the mutational patterns of BRCA1, BRCA2, and PALB2 in Taiwanese breast cancer patients through tumor-only sequencing. This highlights the growing importance of BRCA1/2 and PALB2 alterations in breast cancer susceptibility risk and the treatment of index patients. We also emphasized the need to meticulously annotate variants in cancer-driver genes as well as actionable mutations across multiple databases.

Clinical characteristics and treatment outcomes of invasive ductal and lobular carcinoma: analyses of 54,832 taiwan cancer registry index cases.

PURPOSE: Invasive lobular cancer (ILC) is the second most common histology type of breast cancer followed by invasive ductal carcinoma (IDC). This study aimed to investigate the characteristic, treatment strategies, and clinical outcomes of ILC based on a national population-based cancer registry. METHODS: This study recruited 2671 ILC and 52,215 IDC patients diagnosed between 2011 and 2017 using the Taiwan Cancer Registry (TCR). Correlations between ILC and IDC subgroups were assessed using 1:4 propensity score matching and compared using the χ2 test. Disease free survival(DFS) and overall survival(OS) were estimated using the Kaplan-Meier method with the log-rank test. The risk of disease relapse and mortality were assessed using Cox proportional hazards model. RESULTS: ILC patients had larger tumor sizes, more positive axillary lymph node involvement, lower tumor grade, and higher cancer stage than IDC patients. After matching, ILC patients had a significantly higher rate of receiving mastectomy (58.93% and 53.85%) and positive surgical margin regardless of surgery type. ILC exhibited a significantly higher rate of distant metastasis than IDC(3.67% and 2.93%), but no difference in local recurrence rate, DFS or OS between the two groups. Higher cancer stage, higher grade, and mastectomy were risk factors for disease relapse and cancer-specific mortality. The hormone receptor-positive and HER2 over-expression subtypes were found to be associated with a reduced risk of disease relapse, while only PR positivity was associated with a decreased risk of mortality. (all P-values < 0.05). CONCLUSION: ILC patients had a higher mastectomy rate, higher surgical margin rate and distant metastasis rate than IDC patients. There is no significant difference in DFS or OS between ILC and IDC patients. Mastectomy was associated with poor outcomes regardless of ILC or IDC.

Prevalence of Tumor Genomic Alterations in Homologous Recombination Repair Genes Among Taiwanese Breast Cancers.

PURPOSE: Deleterious germline BRCA1/2 mutations are among the most highly pathogenic variants in hereditary breast and ovarian cancer syndrome. Recently, genes implicated in homologous recombination repair (HRR) pathways have been investigated extensively. Defective HRR genes may indicate potential clinical benefits from PARP (poly ADP ribose polymerase) inhibitors beyond BRCA1/2 mutations. METHODS: We evaluated the prevalence of BRCA1/2 mutations as well as alterations in HRR genes with targeted sequencing. A total of 648 consecutive breast cancer samples were assayed, and HRR genes were evaluated for prevalence in breast cancer tissues. RESULTS: Among 648 breast cancers, there were 17 truncating and 2 missense mutations in BRCA1 and 45 truncating and 1 missense mutation in BRCA2, impacting 3% and 5% of the study population (collectively altered in 6%) with cooccurrence of BRCA1/2 in 7 breast cancers. On the other hand, HRR genes were altered in 122 (19%) breast cancers, while TBB (Talazoparib Beyond BRCA) trial-interrogated genes (excluding BRCA1/2) were mutated in 107 (17%) patients. Beyond BRCA1/2, the most prevalent HRR mutant genes came from ARID1A (7%), PALB2 (7%), and PTEN (6%). Collectively, 164 (25%) of the 648 Taiwanese breast cancer samples harbored at least one mutation among HRR genes. CONCLUSIONS: The prevalence of BRCA1/2 mutations was far below one tenth, while the prevalence of HRR mutations was much higher and approached one-fourth among Taiwanese breast cancers. Further opportunities to take advantage of defective HRR genes for breast cancer treatment should be sought for the realization of precision medicine.

Effects of naturalistic decision-making model-based oncofertility care education for nurses and patients with breast cancer: a cluster randomized controlled trial.

PURPOSE: This study examined the effects of an oncofertility education program on decisional conflict in nurses and patients with breast cancer. METHODS: A cluster randomized controlled trial was conducted with 84 nurses of five breast care units. Three units were randomly selected from the five as the nurse experimental group. Nurses at the experimental group accepted the oncofertility education based on the naturalistic decision-making (NDM) model, while those at the control group accepted the other non-oncofertility education. We also collected data from female patients before and after the nurses' educational training, respectively. The decisional conflict was measured using the Chinese version of the decisional conflict scale. RESULTS: Nurses in the experimental group had less decisional conflict after the oncofertility educational intervention than those in the control group. After the intervention, nurses with higher infertility knowledge scores had significantly lower decisional conflict. Single nurses had significantly higher decisional conflict than married nurses. A higher perceived barrier score was significantly associated with a higher decisional conflict score. Among patients with the same fertility intention scores, those in the experimental group had lower decisional conflict scores than those in the control group. CONCLUSIONS: Our work demonstrates that NDM-based oncofertility care education is feasible and acceptable to improve nurse and patient decisional conflict. Educational training based on the NDM model decreased the decisional conflict regarding oncofertility care. CLINICALTRIALS: gov Identifier: NCT04600869.

Developing a web-based oncofertility tool for reproductive-age women with breast cancer based on social support framework.

PURPOSE: To develop electronic systems for oncofertility support, and to examine the comprehensibility, feasibility, usability, and effects on social support and preparation for decision-making. METHODS: The study steps were guided, tested, and utilized to (a) identify the requirements of a patient, (b) guide the development of support interventions, and (c) evaluate the quality of web-based oncofertility support. Alpha testing and beta testing were used to ensure the quality of the web-based oncofertility support tool. The effectiveness was evaluated using the Preparation for Decision-Making Scale and Social Support Questionnaire. RESULTS: At the alpha testing phase, the mean (± standard deviation) values of the comprehensibility and usability for reproductive-age women with breast cancer were 4.24 (± 0.47) and 4.42 (± 0.57); and the mean values of the acceptability and usability for healthcare providers were 4.04 (± 0.67) and 3.99 (± 0.66), respectively. At the beta testing phase, the mean values of the feasibility for patients and healthcare providers were 3.93 (± 0.67) and 4.17 (± 0.78), respectively. The corresponding mean Preparation for Decision-Making Scale scores were 3.78 ± 0.82 and 4.11 ± 0.93, respectively. The results of the Wilcoxon signed-rank test revealed that the informational and instrumental support scores improved significantly compared with the pre-test data (informational support: 8.94 ± 3.28 vs. 10.06 ± 1.91, p < 0.01; instrumental support: 7.44 ± 2.90 vs. 8.75 ± 2.57, p < 0.01). CONCLUSIONS: The oncofertility support website demonstrated acceptable comprehensibility, feasibility, and usability, in addition to informational and instrumental support. TRIAL REGISTRATION: Clinicaltrials.gov NCT05100498, https://clinicaltrials.gov/ct2/show/NCT05100498.

Long-Term Complications and Patient-Reported Outcomes After Alloplastic Breast Reconstruction.

BACKGROUND: The most widely used method for breast reconstruction in Taiwan is alloplastic breast reconstruction, and traditionally, it can be categorized into immediate or delayed, single-stage or 2-stage procedures. We evaluated clinical outcomes and analyzed patients' self-reported satisfaction and quality of life after alloplastic breast reconstruction based on a previous preliminary study. PATIENT AND METHODS: The patients who underwent primary alloplastic breast reconstruction after mastectomy were recruited in 2006 to 2020 at a single institute in Taiwan. The assessment of clinical outcomes was conducted by retrospective chart review and risk analysis. The patients also completed the BREAST-Q, a condition-specific patient-reported outcome measure, at least 6 months after treatment. RESULTS: A total of 237 patients with 247 reconstructed breasts were enrolled in this study. The demographics showed that 205 (83%) were reconstructed using a 2-stage tissue expander-based procedure and 42 (17%) were 1-stage direct-to-implant reconstructions. The mean follow-up time was 79.5 months. The clinical assessment revealed that the overall complication rate was 34%, with infection being the most common (21 patients; 8%). According to risk analysis, smoking (odds ratio, 7.626; 95% confidence interval, 1.56-37.30; P = 0.012), and nipple-sparing mastectomy (odds ratio, 3.281; 95% confidence interval, 1.54-6.99; P = 0.002) were significant risk factors for overall complications. The questionnaire response rate was 38% (94 of 247), at least 6 months after treatment. The total mean score was 69.78. CONCLUSIONS: At a single institute in Taiwan from 2006 to 2020, alloplastic breast reconstruction, either single- or 2-stage, have acceptable complication rate and good postoperative satisfaction based on patient-reported outcomes. Both patient- and surgery-related factors presented as significant risk factors. Precise patient selection and comprehensive discussion between the patient and physician may play the important role to achieve optimal aesthetic outcomes.

The Effect of Biological Scaffold (Biodesign) in Postmastectomy Direct-to-Implant Breast Reconstruction: A 5-Year Single-Institution Experience.

BACKGROUND: Direct-to-implant (DTI) breast reconstruction is one of the immediate implant-based breast reconstruction methods. If the amount of soft tissue (eg, muscle or fascia) is insufficient to completely cover the implant, biological scaffold or acellular dermal matrix can be safely used for implant coverage. In this study, we used an acellular porcine small intestinal submucosa (SIS) mesh (Biodesign; Cook Medical Inc, Bloomington, IN) for DTI reconstruction to explore the impact of its use on breast reconstruction results. METHODS: We retrospectively assessed cases involving DTI reconstruction at Taipei Veterans General Hospital from 2015 to 2019. Women, 18 years or older, who underwent immediate DTI reconstruction after mastectomy were included in the study. Mastectomy may have been performed because of therapeutic or prophylactic reasons. Patients who did and did not use SIS mesh for reconstruction were studied separately, and the 2 groups were compared in terms of clinical outcomes and complications. The validated, self-administered BREAST-Q Reconstruction Module version 2.0 survey was used to evaluate health-related quality of life and satisfaction among patients who underwent breast reconstruction. RESULTS: A total of 30 DTI breast reconstructions were enrolled. The mean age was 49.2 years, and the mean body mass index was 22.3 kg/m2. The mean postoperative follow-up duration was 17.1 months. Nipple-sparing mastectomy was performed for 26 cases (86.7%), and DTI breast reconstructions using SIS mesh for implant coverage were done in 14 cases (46.7%). The overall complication rate was 53.3% in 30 reconstructions, with nipple complications being the most common complication. The non-SIS and SIS-using groups had a similar overall complication rate postoperatively. As for the quality-of-life assessment, the SIS group obtained a higher score on BREAST-Q than those for whom SIS was not used. CONCLUSIONS: Porcine SIS mesh might be a safe and effective alternative to biological scaffolds in immediate 1-stage implant-based breast reconstruction to improve the quality of life after surgery.

Comprehensive molecular profiling of Taiwanese breast cancers revealed potential therapeutic targets: prevalence of actionable mutations among 380 targeted sequencing analyses.

BACKGROUND: Breast cancer is one of the leading causes of cancer-related deaths in women, and there is a demand in developing an Asian-based genetic profiling database for breast cancer in improving the treatment response. This study aimed to determine molecular alternations and identify potential therapeutic targets by analyzing the genetic profiling from a cohort of Taiwanese breast cancers using a commercialized next-generation sequencing (NGS) targeted panel. METHODS: The study population comprised a broad spectrum of breast cancer patients in Taiwan, including Group 1: planned to receive first-line surgery and followed by adjuvant therapy, or early relapse within three years, Group 2: planned to receive first-line neoadjuvant therapy and followed by surgery, and Group 3: de novo stage IV, or stage IV with recurrence beyond three years. Molecular profiles were determined using Thermo Fisher™ Oncomine™ Comprehensive Assay version 3 (TMO comprehensive assay) from Formalin-Fixed Paraffin-Embedded (FFPE) tissues. Level of actionability was evaluated with the ESMO Scale of clinical actionability of molecular targets (ESCAT). RESULTS: A total of 380 TMO comprehensive assays were conducted on 372 patients, and we presented targeted sequencing analyses of Tier I: alteration-drug match associated with improved outcome in clinical trials including ERBB2 amplification, BRCA1/2 germline mutation, PIK3CA mutation, and NTRK translocation, and Tier II: antitumor activity associated with the matched alteration-drug but lack of prospective outcome data including PTEN loss, ESR1 mutation, AKT1 mutation, and ERBB2 mutation, and Tier III: matched drug-alteration that led to clinical benefit in another tumor type including MDM2 amplification, and ERBB3 mutation. Among them, 249 (66%) showed at least one actionable alternation based on the ESCAT criteria. The most frequent impacted genes (all variants combined within each sample) were PIK3CA (38%), followed by ERBB2 (23%), ESR1 (10%), AKT1 (6%), and BRCA2 (5%), and the remaining rare variants (less than 5% of assayed cohort) were BRCA1 (3%), MDM2 (2.2%), and ERBB3 (1.1%). CONCLUSION: Targeted sequencing of actionable genes is believed to provide clinical applicability and substantial benefits for Taiwanese breast cancer patients. A valid scale of clinical actionability should be adopted for precision medicine practice under multidisciplinary molecular tumor board.

VGH-TAYLOR: Comprehensive precision medicine study protocol on the heterogeneity of Taiwanese breast cancer patients.

Heterogeneity in breast cancer leads to diverse morphological features and different clinical outcomes. There are inherent differences in breast cancer between the populations in Asia and in western countries. The use of immune-based treatment in breast cancer is currently in the developmental stage. The VGH-TAYLOR study is designed to understand the genetic profiling of different subtypes of breast cancer in Taiwan and define the molecular risk factors for breast cancer recurrence. The T-cell receptor repertoire and the potential effects of immunotherapy in breast cancer subjects is evaluated. The favorable biomarkers for early detection of tumor recurrence, diagnosis and prognosis may provide clues for the selection of individualized treatment regimens and improvement in breast cancer therapy.

Lay abstract We describe the rationale and design for the VGH-TAYLOR study, which includes Taiwanese patients with breast cancer and with a wide spectrum of clinical scenarios covering different breast cancer subtypes and clinical settings, such as the neoadjuvant, adjuvant and metastatic settings. The gene expression profile and genetic mutations of breast cancer subjects with the primary and recurrent tumors are compared. We also explore whether immune-related gene expression and diversity have any impact on response to treatment and survival. This study aims to discover biomarkers of detection of cancer relapse, diagnosis and prognosis that may enable personalized medicine and improvement in breast cancer treatment. Clinical trial registration: NCT04626440 (ClinicalTrials.gov).

Developing a Web-Based Shared Decision-Making Tool for Fertility Preservation Among Reproductive-Age Women With Breast Cancer: An Action Research Approach.

BACKGROUND: The pregnancy rate after cancer treatment for female survivors is lower than that of the general population. Future infertility is a significant concern for patients with breast cancer and is associated with a poor quality of life. Reproductive-age patients with breast cancer have safe options when choosing a type of fertility preservation method to be applied. Better information and support resources aimed at women to support their decision making are needed. OBJECTIVE: The objective of this study was to develop a web-based shared decision-making tool for helping patients with breast cancer make decisions on fertility preservation. METHODS: We used the action research cycle of observing, reflecting, planning, and acting to develop a web-based shared decision-making tool. The following four phrases were applied: (1) observe and reflect-collect and analyze the decision-making experiences of patients and health care providers; (2) reflect and plan-apply the initial results to create a paper design and modify the content; (3) plan and act-brainstorm about the web pages and modify the content; (4) act and observe-evaluate the effectiveness and refine the website's shared decision-making tool. Interviews, group meetings, and constant dialogue were conducted between the various participants at each step. Effectiveness was evaluated using the Preparation for Decision-Making scale. RESULTS: Five major parts were developed with the use of the action research approach. The Introduction (part 1) describes the severity of cancer treatment and infertility. Options (part 2) provides the knowledge of fertility preservation. The shared decision-making tool was designed as a step-by-step process (part 3) that involves the comparison of options, patient values, and preferences; their knowledge regarding infertility and options; and reaching a collective decision. Resources (part 4) provides information on the hospitals that provide such services, and References (part 5) lists all the literature cited in the website. The results show the web-based shared decision-making meets both patients' and health providers' needs and helps reproductive-age patients with breast cancer make decisions about fertility preservation. CONCLUSIONS: We have created the first web-based shared decision-making tool for making fertility preservation decisions in Taiwan. We believe female patients of reproductive age will find the tool useful and its use will become widespread, which should increase patient autonomy and improve communication about fertility preservation with clinicians. TRIAL REGISTRATION: Clinicaltrials.gov NCT04602910; https://clinicaltrials.gov/ct2/show/NCT04602910.

HER2 immunohistochemical scores provide prognostic information for patients with HER2-type invasive breast cancer.

AIMS: Invasive breast cancer patients with human epidermal growth factor receptor 2 (HER2) immunohistochemical (IHC) scores of 3+ or 2+ with reflex in-situ hybridisation (ISH) positivity are suitable for anti-HER2 therapies. The aim of this study is to investigate whether the prognoses between IHC 3+ patients and IHC 2+/ISH+ patients are different. METHODS AND RESULTS: We analysed the clinicopathological information of 886 consecutive cases of HER2-positive early breast cancer. The influences of the patients' age, cancer stage, hormone receptor status and anti-HER2 treatment were adjusted using a multivariate Cox regression model. Both HER2 copy numbers and HER2 ISH ratios of the IHC 3+ group were significantly higher than those of the IHC 2+/ISH+ group. The outcomes of IHC 3+ patients were significantly better than those of IHC 2+/ISH+ patients in the univariate and multivariate analyses. HER2 copy numbers of ≥8 represented the best prognostic value, and it was chosen to be the cut-off value. The reflex ISH for IHC 2+ patients with high HER2 copy numbers (≥8) predicted a better overall survival than that for those with low HER2 copy numbers. CONCLUSION: HER2 IHC scores and HER2 copy numbers can provide prognostic information for patients with HER2-positive invasive breast cancer. Both IHC 3+ and IHC 2+ patients with high HER2 copy numbers had a better prognosis.

Infertility-related knowledge in childbearing-age women with breast cancer after chemotherapy.

AIM: The purposes of this study were to describe the degree of knowledge and explore the factors associated with knowledge of infertility among women of childbearing age with breast cancer. METHODS: In this cross-sectional study, we recruited women of childbearing age with a diagnosis of breast cancer who had completed chemotherapy at a hospital in Taipei from 2015 through 2016. Face-to-face interviews were completed with 201 (62%) of 324 eligible women, asking about sociodemographic variables, disease and treatment characteristics, fertility intention, and infertility-related knowledge. RESULTS: The result showed one in 10 women had thought about becoming pregnant after completion of breast cancer chemotherapy. The mean score of infertility knowledge among participants was low, especially for general knowledge. Women with higher levels of education had better knowledge scores. Fertility intention score, especially for the domain of the pregnant risk, was negatively associated with infertility knowledge score. CONCLUSION: Women with breast cancer lacked knowledge about infertility and underestimated the possibility of infertility. We suggest future patient education on infertility after cancer treatment and about reproductive technology in oncologic practice before treatment begins.

Oncofertility to Evidence-Based Practice: Changes in Fertility Intention and Symptom Burden in Reproductive-Age Women With Breast Cancer.

BACKGROUND: Infertility is negatively related to the quality of life in reproductive-age women with breast cancer. The nurses who care for these patients lack a comprehensive understanding of the changes in fertility intention that patients undergo from the time of cancer diagnosis, throughout treatment, and after treatment. A fertility intention assessment is the first step in discerning the patient's ideas toward future pregnancy. AIMS: This study examined the changes in fertility intention and symptom burden in reproductive-age women with breast cancer before, during, and after treatment. We also explored predictors of fertility intention among the women. METHODS: The study was guided by the theory of planned behavior. A longitudinal and observational study was conducted with 151 women with breast cancer who were treated at a teaching hospital in Taipei. The participants were interviewed using a structured questionnaire before, during, and after chemotherapy from July 2016 to March 2018. Fertility intention was assessed using the Fertility Intention Scale. The M.D. Anderson Symptom Inventory-Taiwanese version was used to measure the symptom burden. The generalized linear mixed model was used for multivariate analysis. RESULTS: Patients had significantly lower scores for fertility intention after treatment than before treatment. The study patients had substantially worse symptom burden during treatment than before or after treatment. Symptom burden scores, especially for symptom interference, correlated significantly with fertility intention. A higher Fertility Intention Scale score was significantly associated with younger age. LINKING EVIDENCE TO ACTION: Fertility intention decreased over time in women with breast cancer. Understanding fertility intention and controlling symptom burden throughout the course of treatment and beyond might help nurses provide better care for preserving fertility and maintaining fertility options for these women with breast cancer.

Prevalent landscape of tumor genomic alterations of luminal B1 breast cancers using a comprehensive genomic profiling assay in Taiwan.

BACKGROUND: The human epidermal growth factor receptor 2 (HER2) negative luminal B1 subtype of breast cancer has been reported with a poorer outcome than luminal A in recent studies. This study aimed to investigate the molecular alterations and identify potential therapeutic targets by analyzing the genetic profiling from a cohort of luminal B1 breast cancer in Taiwan. METHODS: We enrolled patients with luminal B1 breast cancer in our study. They were classified as patients who received curative surgery and adjuvant or neoadjuvant chemotherapy as the low-risk group, and who had advanced or metastatic disease or early relapse during the follow-up time as the high-risk group. Using targeted sequencing, we evaluated genomic alterations, interpreting variants with the ESMO Scale of clinical actionability of molecular targets (ESCAT). RESULTS: A total of 305 luminal B1 breast cancer patients underwent targeted sequencing analyses. The high-risk patients reported more actionable genes and called variants than the low-risk group (P < 0.05). PIK3CA (42%), FGFR1 (25%), and BRCA1/2 (10.5%) were the most prevalent ESCAT actionable alterations in luminal B1 breast cancer. There was no difference in the prevalence of actionable mutations between these two groups, except for ERBB2 oncogenic mutations, which were more prevalent among the high-risk than the low-risk group (P < 0.05). Alterations in PTEN, ERBB2, and BRCA1/2 were associated with disease relapse events in luminal B1 breast cancer. CONCLUSIONS: PIK3CA, FGFR1, and BRCA1/2 were the most prevalent actionable alterations among Taiwanese luminal B1 breast cancer. Moreover, PTEN and BRCA1/2 was significantly associated with disease relapse.

Real-world experience with CDK4/6 inhibitors in hormone receptor-positive metastatic and recurrent breast cancer: findings from an Asian population.

PURPOSE: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) combined with endocrine therapy have demonstrated significant clinical benefits in progression-free and overall survival. This study investigates the outcomes associated with two kinds of CDK4/6i in patients with hormone receptor (HR)-positive metastatic and relapsed breast cancer to inform real-world evidence of treatment strategies. METHODS: This retrospective study included 340 Taiwanese patients with HR-positive advanced breast cancer from the Taipei Veterans General Hospital, between 2018 and 2023. We analyzed patient characteristics, treatment strategies and outcomes associated with two CDK4/6i. The efficacy of patients who experienced economic burden and interrupted CDK4/6i treatment after 2 years of National Health Insurance (NHI) reimbursement was also investigated. RESULTS: Patients receiving ribociclib and palbociclib showed no significant differences in age, histology, body mass index(BMI), or pathologic status. The distribution of disease status and endocrine therapy partners was comparable between the two groups. Dose reduction was similar, while patients with palbociclib tended to discontinue CDK4/6i usage, and those with ribociclib tended to switch to the other CDK4/6i or endocrine partners. There was no significant difference in progression-free survival (PFS) between the two CDK4/6i in the first-line setting. Adverse prognostic factors were increasing HER2 IHC score, higher Ki-67 levels, visceral and liver metastasis, prior chemotherapy, and endocrine therapy resistance, while higher BMI, bone-only metastasis, and letrozole treatment were associated with a lower risk of progression. The limited follow-up time in our study was insufficient to assess the outcomes of patients treated with interrupted CDK4/6i for up to two years under the NHI reimbursement policy. CONCLUSION: Treatment outcomes between the two types of CDK4/6i did not differ significantly, indicating the safety and efficacy of CDK4/6i for the Asian population. Ribociclib and palbociclib showed similar efficacy in PFS in the real-world setting.

Clinical outcomes and patient-reported outcomes after oncoplastic breast surgery in breast cancer patients: A matched cohort study.

BACKGROUND: Surgery is the recommended treatment for breast cancer, the most common cancer in women in Taiwan and the leading cause of cancer-related deaths. Although breast-conserving surgery (BCS) has good prognosis, in some cases, BCS may cause more significant deformities and interfere with the patient's psychosocial well-being. Oncoplastic breast surgery (OBS) is the treatment option in these cases. This study aimed to determine the outcomes of OBS and BCS regardless of clinical and patient-reported esthetic outcomes. METHODS: Between 2015 and 2020, 50 patients who underwent OBS at our hospital after complete treatment were enrolled. With 1:2 matched ratios, 100 patients were enrolled in the BCS control group. Clinical outcomes were analyzed. The BREAST-Q questionnaire was then assessed 6 months after the completion of treatment for subjective patient-reported outcomes. RESULTS: Due to the matching process, no difference was noted between the two groups in terms of demographic data such as age, comorbidities, or tumor characteristics. There were no significant differences in the local recurrence rate, disease-free survival, overall survival, positive margin rate, rewide excision rate, conversion to mastectomy rate, or complication rate (major or minor) between both groups. However, the OBS group showed higher satisfaction with breasts in the BREAST-Q questionnaire ( p < 0.001). The mean follow-up time was 38.77 ± 14.70 months in the BCS group and 29.59 ± 14.06 months in the OBS group. CONCLUSION: OBS seems to be a safe and feasible surgery in breast cancer patients because clinical outcomes are compatible with BCS. Moreover, the OBS group had better patient-reported outcomes in terms of satisfaction.

Impacts of HER2 immunohistochemical scores on response and outcomes of HER2-positive breast cancers after neoadjuvant therapy.

BACKGROUND: Neoadjuvant systemic therapy (NST) is conducted in increased number of patients with breast cancer overexpressing human epidermal growth factor receptor 2 (HER2). Whether the intensity of HER2 protein expression determines response to treatment is challenged. This study aims to analyze the impact of HER2 immunohistochemical (IHC) scores on NST response and survival outcome. METHODS: We analyzed a total of 197 patients with HER2-positive breast cancer receiving NST and definite surgery from a prospectively collected database. The analyzed endpoints included pathological complete response (pCR), disease-free survival (DFS), and overall survival (OS). More patients with IHC 2+/ in situ hybridization (ISH)-positive tumors presented positive for hormonal receptors, compared with those with IHC 3+ tumors. No clinicopathological features except tumor necrosis were significantly associated with pCR. RESULTS: Both positive hormone receptors and IHC scores stood on the borderline in statistical analysis. IHC 3+ group tends to present a higher pCR rate than IHC 2+/ISH+ groups (52.5% vs. 34.3%). Patients who achieved pCR had better survival outcome than that of non-pCR group. The impact of pCR on survival reached the statistical significance in the IHC 3+ group both in DFS (90.9% vs. 76.5%; p = 0.004) and OS (97.4% vs. 83.2%; p = 0.002). Multivariate analysis demonstrated IHC scores as an independent predictor of survival outcome with the adjustment of tumor staging and pCR. CONCLUSION: HER2 IHC score is an independent predictor for outcome. IHC 3+ tumors presented a trend of higher pCR rate and better outcome in HER2-positive breast cancer patients who receive NST.

Prevalence of PIK3CA mutations in Taiwanese patients with breast cancer: a retrospective next-generation sequencing database analysis.

Background: Breast cancer is the most common cancer type that affects women. In hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) is the most frequently mutated gene associated with poor prognosis. This study evaluated the frequency of PIK3CA mutations in the Taiwanese breast cancer population. Methodology: This is a retrospective study; patient data were collected for 2 years from a next-generation sequencing database linked to electronic health records (EHRs). The primary endpoint was the regional prevalence of PIK3CA mutation. The secondary endpoints were to decipher the mutation types across breast cancer subtype, menopausal status, and time to treatment failure after everolimus (an mTOR inhibitor) or cyclin-dependent kinase 4/6 (CDK4/6) inhibitor treatment. Results: PIK3CA mutations were identified in 278 of 728 patients (38%). PIK3CA mutations were reported in 43% of patients with HR-/HER2+ subtype and 42% of patients with HR+/HER2- postmenopausal status. A lower prevalence of PIK3CA mutations was observed in triple-negative (27%) and HR+/HER2- premenopausal patients (29%). The most common mutation was at exon 20 (H1047R mutation, 41.6%), followed by exon 9 (E545K mutation, 18.9% and E542K mutation, 10.3%). Among patients treated with CDK4/6 inhibitors, the median time to treatment failure was 12 months (95% CI: 7-21 months) in the PIK3CA mutation cohort and 16 months (95% CI: 11-23 months) in the PIK3CA wild-type cohort, whereas patients receiving an mTOR inhibitor reported a median time to treatment failure of 20.5 months (95% CI: 8-33 months) in the PIK3CA mutation cohort and 6 months (95% CI: 2-9 months) in the PIK3CA wild-type cohort. Conclusion: A high frequency of PIK3CA mutations was detected in Taiwanese patients with breast cancer, which was consistent with previous studies. Early detection of PIK3CA mutations might influence therapeutic decisions, leading to better treatment outcomes.