Background

In current clinical practice, the routine approaches of axillary lymph node (ALN) status evaluation through sentinel lymph node biopsy (SLNB) is unsatisfied with high false-negative rate and brings significant complications. We aimed to develop a preoperative magnetic resonance imaging radiomic-based signature for predicting ALN metastasis (ALNM) in a non-invasive way.

Methods

A total of 1,090 early-stage invasive breast cancer patients from 4 institutions were enrolled in this multicenter, retrospective, diagnositc study. Radiomic signature for ALNM prediction were constructed by machine learning in 803 patients from Sun Yat-sen Memorial Hospital and Sun Yat-sen University Cancer Center (Training cohort). The clinical-radiomic siganture was constructed by combining radiomic signature and significant clinic-pathological risk factors and was validated in patients from prospective phase III trials [NCT01503905] (Internal validation cohort, n=106), and Shunde Hospital and Tungwah Hospital (External validation cohort, n=181). This study is registered with ClinicalTrials.gov (NCT04003558) and Chinese Clinical Trail Registry (ChiCTR1900024020).

Results

The radiomic signature for predicting ALNM consisted of intratumoral and ALN features showed AUCs of 0.91, 0.88, and 0.85 in the training, internal validation and external validation cohorts. The clinical-radiomic signature achieved the highest AUCs of 0.93, 0.91, and 0.91 in the training, internal validation and external validation cohorts, which successfully discriminate high- from low risk relapse patients (HR 0.12, 95% CI 0.03–0.53; P<0.001) and was similar to the performance in ALNM and non-ALNM (HR 0.28, 95% CI 0.09–0.87; P=0.002). In additon, the clinical-radiomic signature also performed well in the subgroup of N1, N2, N3 status (AUCs of 0.89, 0.90, 0.97).

Conclusions

This study developed a clinical-radiomic signature incorporated the intratumoral and ALN radiomic features and clinical risk factors, which could serve as a non-invasive tool to evaluate ALN status for guiding surgery plans of early-stage breast cancer patients.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Fertility and pregnancy-related issues are a priority area of concern for young breast cancer (BC) patients (pts). Limited evidence exists on knowledge, practice and attitudes of physicians practicingin low- and middle-income countries (LMIC)towards these issues.

Methods

A 19-item questionnaire adapted from an international survey (Lambertini et al, Breast 2018) exploring issuesaboutfertility preservation and pregnancy after BCwas sent by email to physicians from LMIC involved in BC care.Descriptive analyses were performed.

Results

A total of 288 physicians completed the survey. Median age was 38 years (interquartile range 33-45).Respondents from Asia, Africa, America and Europe filled in the survey: the 3 most represented countries were Mexico (27.1%), India (18.4%) and Brazil (8.3%).The majority of respondents were medical oncologists (44.4%)working in an academic setting (46.9%). Among respondents, 40.2% and 53.8% reported never having consulted the available international guidelines on fertility preservation and pregnancy after BC, respectively. 25.0%, 19.1% and 24.3% of respondents declared to be not at all knowledgeable about embryo, oocyte or ovarian tissue cryopreservation, respectively. 29.2%, 23.6% and 31.3% declared that embryo, oocyte and ovarian tissue cryopreservation are not available in their countries, respectively. 57.6% of respondents disagreed or were neutral on the statement that controlled ovarian stimulation (COS) can be considered safe in BC pts; 29.9%suggested that COS should not be considered safe in pts with hormone receptor-positive (HR+) disease. 49.7% and 58.6% of respondents agreed or were neutral on the statement that pregnancy in BC survivors may increase the risk of recurrence overall or only in those with HR+ disease, respectively. In contrast, 49.0% agreed that COS in BC survivors can be safely considered.

Conclusions

Several misconceptions exist among physicians from LMIC on fertility and pregnancy-related issues in young BC pts. Increased awareness and further educational initiatives are needed to improve adherence to available guidelines and pts’oncofertility counseling.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N.F. Ponde: Advisory/Consultancy: Lilly; Honoraria (self): Roche,Novartis, AstraZeneca and Lilly. M. Brandão: Honoraria (self), Travel/Accommodation/Expenses: Roche/GNE. I.B. Spasojevic: Advisory/Consultancy: Roche, Novartis, Amicus; Honoraria (self): Roche, Novartis, Pfizer, AstraZeneca. A. Odhiambo: Honoraria (self), Travel/Accommodation/Expenses: AstraZeneca, Roche, Novartis; Advisory/Consultancy: Pfizer, AstraZeneca, Janssen. M. Tagliamento: Travel/Accommodation/Expenses: Roche, Bristol-Myers Squibb, AstraZeneca, Takeda; Full/Part-time employment, Medical Writer: Novartis, Amgen. M. Lambertini: Advisory/Consultancy: Roche, Novartis; Honoraria (self): Roche, Takeda, Theramex, Novartis, Pfizer, Lilly. All other authors have declared no conflicts of interest.

Background

Women with HR+(ER and/or PR positive) in early breast cancer usually have a better outcome than other cancer variants. However, as the patient age, there were few reports on the survival status of elderly women in HR+ early breast cancer and concomitant diseases. Base on a large-scale population, the results of statistical analysis would aid in clinical decisions and effective interventions on the treatment of elderly patients.

Methods

Based on the Surveillance, Epidemiology, and End Results (SEER) database, elderly (age≥60) female patients diagnosed HR+ early breast cancer from 2010 to 2016 were included. They were divided into two groups: elderly patients (age 60-74, group A) and senior elderly patients (age≥75, group B). Kaplan-Meier survival analysis was used to compare the 5-year overall survival (OS) rate, cumulative mortality, and the proportion cause of death.

Results

In total there were 147,969 cases were included, which were 100,091 cases in group A and 47,878 cases in group B. The 5-year OS in group A and B were 89.9% vs. 68.8% (HR 3.53, 95% CI 3.43-3.64, P < 0.001) respectively. The proportion of HER2- and HER2+ cases in group A were 90.2% and 9.8%, which 5-year OS were 90.2% vs. 87.7% (HR 0.77, 95% CI 0.72-0.83, P < 0.001). The proportion of HER2- and HER2+ cases in group B were 91.9% and 8.1%, which 5-year OS were 69.5% vs. 61.0% (HR 0.70, 95%CI 0.66-0.75, P < 0.001). There was no significant difference in cumulative mortality between breast and non-breast cancer related deaths (HR: 0.98, 95% CI 0.93-1.03, P = 0.4) in group A; but that was significantly difference in group B (HR: 0.77, 95% CI 0.733-0.799, P < 0.001). The primary non-breast related death in group A were diseases of the heart (12.1%), COPD and related conditions (4.8%); while in group B that were diseases of the heart (20.43%) and cerebrovascular disease (5.4%).

Conclusions

The risk of death in elderly HR+ early breast cancer patients was relatively increasing with age, especially the death caused by cardiovascular and cerebrovascular events. HR+/HER2+ patients have a higher risk of death requiring further intensive treatment. The age-related comorbidity risk and breast cancer subtypes should be considered in the treatment of these patients to make a comprehensive treatment decision.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

In the early stages, the use of neo-adjuvant systemic treatment is the standard of care in TNBCs. Patients who achieve a pathological complete response (pCR) have improved survival outcomes. The programmed cell death receptor ligand, PD-L1, has been shown to have high expression in TNBCs. To date, major research efforts are being undertaken to determine the applicability of PD-1/PD-L1 immune checkpoint inhibitors in TNBC.

Methods

A systematic search of Pubmed, Embase, Cochrane, Clinical trials databases and hand search were utilized to identify RCTs investigating the use of neoadjuvant PD-1/PD-L1 inhibitors plus standard chemotherapy in TNBC. Trials that were published up to March 2020 were included and were appraised. Using the random effects model, pooled Odds ratios (ORs) with 95% confidence intervals (CI) were calculated for pCR. Subgroup analysis of pCR rates based on PD-L1 expression was also done.

Results

Four RCTs were included (N=384). The addition of immunotherapy to chemotherapy in the neo-adjuvant setting showed significant pCR benefit of 58.5% vs 42.2% compared to chemotherapy alone (OR 1.76, 95% CI 1.11-2.79, P <0.02). Subgroup analysis based on PD-L1 expression showed that in the immunotherapy plus chemotherapy group, there is a significantly higher pCR rate in the PD-L1-positive population than in the PD-L1 negative group (64.5% vs 39.4%). The addition of immunotherapy showed a significant benefit in improving pCR in the PD-L1-positive group (OR 1.55, 95%CI 1.16-2.09, p = 0.003, I2 =0%).

Conclusions

The addition of PD-1/PD-L1 inhibitors to standard chemotherapy is associated with increased pCR rates in patients with TNBC, hence, supporting its use for patients in the neo-adjuvant setting. Subgroup analysis showed that the benefit of adding immunotherapy was more significant in those with PD-L1-expressing tumors. This result indicates that the PD-L1 immune marker may have utility in selecting TNBC patients who can benefit more from PD-L1 inhibitors. Longer follow-up and further analysis of these studies would hopefully demonstrate significance in other outcomes such as progression-free survival and overall survival.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.

Background

Epidemiologic findings suggested that bipolar disorder (BD) may be associated with increased risk of breast cancer. However, there are few studies that comprehensively evaluate their correlation and the causal effect remains unknown. With a Mendelian randomization (MR) approach, we were able to investigate the causal relationship between genetically predicted BD and breast cancer risk.

Methods

Utilizing 6 BD-related single nucleotide polymorphisms as instrumental variables identified by the latest genome-wide association studies, we investigated the correlation between genetically predicted BD and breast cancer risk using summary statistics from the Breast Cancer Association Consortium, with a total of 122 977 cases and 105 974 controls. Study-specific estimates were summarized using inverse-variance-weighted (IVW) method. To further evaluate the pleiotropy, the weighted median and the MR-Egger regression method were implemented. Subgroup analyses according to different immunohistochemical type of breast cancer were also conducted.

Results

MR analyses demonstrated that genetically predicted BD was causally associated with an increased risk of breast cancer (OR = 1.058; 95% CI 1.023-1.093, p < 0.001). When results were examined by immunohistochemical type, a strong association was observed between genetically predicted BD and estrogen receptor-positive (ER) breast cancer (OR = 1.048, 95%CI 1.008-1.090 p = 0.0177) rather than ER-negative breast cancer (OR = 1.026, 95%CI 0.975-1.081 p = 0.3231). Additionally, the results demonstrated the absence of the horizontal pleiotropy. Table: 11P

Mendelian randomization estimates of the associations between bipolar disorder and risk of breast cancer overall and immunohistochemical types

Conclusions

Our findings provide evidence for a causal relationship between genetically predicted BD and increased breast cancer risk, overall and among specific immunohistochemical type. Further studies are warranted to investigate the underlying mechanism.

Legal entity responsible for the study

Haoxin Peng.

Funding

China National Science Foundation (Grant No. 81871893); Key Project of Guangzhou Scientific Research Project (Grant No. 201804020030); Cultivation of Guangdong College Students' Scientific and Technological Innovation (“Climbing Program” Special Funds) (Grant No. pdjh2020a0480).

Disclosure

All authors have declared no conflicts of interest.