Tumor-infiltrating lymphocytes (TILs) evaluated in primary breast cancer (BC) convey prognostic information. Limited data in the metastatic setting are available.
Secondary lesions from 94 BC ...patients, 43 triple-negative (TN) and 51 HER2-positive, were evaluated for TILs and expression of CD8, FOXP3, and PD-L1 by immunohistochemistry.
TILs levels on metastasis were generally low (median 5%) and did not differ between TN and HER2+ tumors. Younger patients showed significantly lower TILs (p = 0.002). In HER2+ patients, TILs were higher in lung metastases as compared to other sites (p = 0.038). TILs composition was different across metastatic sites: skin metastases presented higher FOXP3 (p = 0.002) and lower CD8/FOXP3 ratio (p = 0.032). Patients treated for metastatic BC prior to biopsy had lower CD8 (overall: p = 0.005, HER2+: p = 0.011, TN: p = 0.075). In TN patients, median overall survival (OS) was 11.8 and 62.9 months for patients with low and high TILs, respectively (HR 0.29, 95%CI 0.11-0.76, log-rank p = 0.008). CD8/FOXP3 ratio was also prognostic in TN patients (median OS 8.0, 13.2, and 54.0 months in 1st, 2nd and 3th tertile, log-rank p = 0.019). Both TILs and CD8/FOXP3 ratio were independent factors at multivariate analysis. Counterintuitively, in HER2+ BC, low TILs tumors showed better prognosis (median OS 53.7 vs 39.9 months in TILs low and TILs high, not statistically significant).
Our findings indicate the relevance of TILs as prognostic biomarker for TNBC even in the advanced setting and provide novel hypothesis-generating data on potential sources of immune heterogeneity of metastatic BC.
Background
Current guidelines recommend adjuvant chemotherapy for patients with small, lymph node–negative, triple‐negative breast cancer (TNBC) measuring >5 mm (T1b disease), but clinical evidence ...to support this recommendation is lacking. Thus, the current study aimed to evaluate the survival benefit of adjuvant chemotherapy in patients with T1N0M0 (measuring ≤2 cm) TNBC with different tumor sizes.
Methods
The authors retrospectively evaluated consecutive patients with pT1N0M0 TNBC who were diagnosed between 2000 and 2016 at Sun Yat‐Sen University Cancer Center. For the meta‐analysis, electronic medical databases were searched for all relevant studies regarding the effect of adjuvant chemotherapy on the target population.
Results
Of the 351 enrolled patients, 309 (88%) received adjuvant chemotherapy and 42 patients (12%) did not. The distribution by T classification was T1a in 19 patients (5.4%), T1b in 67 patients (19.1%), and T1c in 265 patients (75.5%). Adjuvant chemotherapy significantly improved recurrence‐free survival (RFS) in the patients with T1c disease, but not those with T1b and T1a disease. Meanwhile, there was no difference in RFS noted according to the chemotherapy regimen among patients with T1c disease. Seven eligible studies comprising 1525 patients with T1N0M0 (941 with T1a/bN0M0) were included in the meta‐analysis. The meta‐analysis demonstrated that adjuvant chemotherapy significantly reduced the rate of disease recurrence for patients with T1a/b disease as a group, but the population driving that was only patients with T1b disease, not those with T1a disease.
Conclusions
Although the retrospective analysis demonstrated a survival benefit of adjuvant chemotherapy only for patients with T1cN0 TNBC, the meta‐analysis showed it also is beneficial for individuals with T1bN0 TNBC. For patients with T1cN0M0 TNBC, less intensive chemotherapy regimens achieve an excellent survival outcome similar to that of intensive anthracycline and taxane combination chemotherapy.
The current study evaluates the survival benefit of adjuvant chemotherapy in the treatment of patients with T1N0M0 triple‐negative breast cancer (TNBC) with different tumor classifications based on single‐center data and a meta‐analysis of the published literature. The authors conclude that adjuvant chemotherapy yields a survival benefit not only among patients with T1cN0M0 TNBC, but also those with T1bN0M0 disease, thereby providing instrumental evidence to support current treatment guidelines.
Background
Patients with newly diagnosed breast cancer and high levels of anxiety often pursue more aggressive surgical interventions. The neoadjuvant treatment (NAT) setting could provide a window ...of opportunity to address patients’ anxiety. However, the impact of anxiety on surgical decisions in the setting of NAT for breast cancer has not been previously studied.
Materials and Methods
A prospective database of patients with breast cancer treated with NAT at BC Cancer was used to identify patients treated with NAT and subsequent surgical resection. Patients with bilateral breast cancer or BRCA mutations or those referred to the hereditary cancer program were excluded. An anxiety score of 0–3 was assigned based on responses to the Edmonton Symptom Assessment System and Psychosocial Screen for Cancer. Clinicopathological information and treatment data were retrieved and cross‐referenced between the low‐anxiety (scores 0–1) and high‐anxiety (scores 2–3) cohorts.
Results
From 2012 to 2016, 203 patients met eligibility criteria. Of these, 93 patients (45.8%) had low anxiety and 110 patients (54.2%) had high anxiety. Overall, 161 patients (79.3%) had locally advanced cancers; no differences in stage, grade, or biomarkers were found between the low‐ and high‐anxiety cohorts. Patients with high self‐reported anxiety at initial consultation were younger (mean 56 years vs. 60 years; p = .011) and more likely to undergo mastectomy for breast‐conserving surgery–eligible disease and bilateral mastectomy for unilateral disease compared with those with low anxiety (37.3% vs. 18.3%; likelihood ratio 9.15; p = .002). No significant differences in treatment timelines were identified between the two cohorts.
Conclusion
Patients with high anxiety at initial consultation were nine times more likely to undergo aggressive surgery compared with patients with low anxiety. These findings underscore the need for early identification of patients who may benefit from tailored supportive and educational services to address sources of anxiety and knowledge gaps.
Implications for Practice
The prevalence of anxiety among women with newly diagnosed breast cancer is being increasingly acknowledged. However, health care providers have not fully appreciated the impact of anxiety on the surgical management of patients with early‐stage breast cancer. This study highlights the importance of self‐reported anxiety on surgical management. The preoperative period provides a unique window of opportunity to address sources of anxiety and provide targeted educational materials over a period of 4–6 months, which may ultimately lead to less aggressive surgery when it is not needed.
This article reviews the effect of patient anxiety on decisions related to surgical treatment of early stage breast cancer and the use of self‐reported anxiety as a clinical tool to tailor educational and supportive resources.
The aim of the study was to develop and validate a deep learning radiomic nomogram (DLRN) for preoperatively assessing breast cancer pathological complete response (pCR) after neoadjuvant ...chemotherapy (NAC) based on the pre- and post-treatment ultrasound.
Patients with locally advanced breast cancer (LABC) proved by biopsy who proceeded to undergo preoperative NAC were enrolled from hospital #1 (training cohort, 356 cases) and hospital #2 (independent external validation cohort, 236 cases). Deep learning and handcrafted radiomic features reflecting the phenotypes of the pre-treatment (radiomic signature RS 1) and post-treatment tumour (RS2) were extracted. The minimum redundancy maximum relevance algorithm and the least absolute shrinkage and selection operator regression were used for feature selection and RS construction. A DLRN was then developed based on the RSs and independent clinicopathological risk factors. The performance of the model was assessed with regard to calibration, discrimination and clinical usefulness.
The DLRN predicted the pCR status with accuracy, yielded an area under the receiver operator characteristic curve of 0.94 (95% confidence interval, 0.91–0.97) in the validation cohort, with good calibration. The DLRN outperformed the clinical model and single RS within both cohorts (P < 0.05, as per the DeLong test) and performed better than two experts' prediction of pCR (both P < 0.01 for comparison of total accuracy). Besides, prediction within the hormone receptor–positive/human epidermal growth factor receptor 2 (HER2)–negative, HER2+ and triple-negative subgroups also achieved good discrimination performance, with an AUC of 0.90, 0.95 and 0.93, respectively, in the external validation cohort. Decision curve analysis confirmed that the model was clinically useful.
A deep learning–based radiomic nomogram had good predictive value for pCR in LABC, which could provide valuable information for individual treatment.
•A novel preoperative pathological complete response prediction model was developed.•The model is based on pre- and post-neoadjuvant chemotherapy ultrasound images.•It yielded an area under the receiver operator characteristic curve AUC of 0.94 in the independent external validation cohort.•It outperformed two experts who evaluated the pathological complete response status.•It may facilitate tailoring the optimum extent of breast and axillary surgery.
Purpose of Review
Platinum compounds are used in the treatment of various types of cancer. Here, we review the current role of cisplatin and carboplatin in the treatment of early stage and advanced ...triple-negative breast cancer (TNBC), and the use of biomarkers in predicting response to platinum therapy.
Recent Findings
Addition of carboplatin to a neoadjuvant chemotherapy regimen can result in improvement in the pathological complete response rates. The long-term benefit of the addition of carboplatin to standard chemotherapy regimens remains unproven. Single-agent platinum is an option in the treatment of advanced breast cancer.
BRCA1/2
mutations predicted benefit from platinums in advanced, but not early stage breast cancer. There are yet no biomarkers to predict response to platinum in sporadic TNBC.
Summary
Platinum compounds are an option in the treatment of TNBC. Identification of biomarkers to select tumors most likely to derive benefit from these agents is still needed. Ongoing trials are exploring the role of platinum in the adjuvant setting and in combination with other agents, including immune checkpoint inhibitors.
A brand new approach to the understanding of breast cancer (BC) is urgently needed. In this contribution, the etiology, pathogenesis, and treatment of this disease is approached from the new ...pH-centric anticancer paradigm. Only this unitarian perspective, based upon the hydrogen ion (H
) dynamics of cancer, allows for the understanding and integration of the many dualisms, confusions, and paradoxes of the disease. The new H
-related, wide-ranging model can embrace, from a unique perspective, the many aspects of the disease and, at the same time, therapeutically interfere with most, if not all, of the hallmarks of cancer known to date. The pH-related armamentarium available for the treatment of BC reviewed here may be beneficial for all types and stages of the disease. In this vein, we have attempted a megasynthesis of traditional and new knowledge in the different areas of breast cancer research and treatment based upon the wide-ranging approach afforded by the hydrogen ion dynamics of cancer. The concerted utilization of the pH-related drugs that are available nowadays for the treatment of breast cancer is advanced.
Breast cancer (BC) is the leading cause of cancer mortality in Pakistan and other South Asian countries. Recent statistics indicate an increased risk of BC incidence and mortality among women in this ...region. Many factors have been associated with increased mortality from this disease including late detection due to inadequate knowledge of screening, and financial constraints due to which many women do not undergo screening tests. Other causes that have led to the deterioration of the disease status among females include a lack of public knowledge of BC's symptoms and misconceptions taking root from cultural reasons. This situation has called into question the effectiveness of BC awareness campaigns, as they may not have achieved the desired results that were originally envisioned. In this paper, we highlight the shortcomings of the awareness campaigns in Pakistan: lack of BC knowledge, financial constraints, and inaccessible healthcare facilities; and suggest alternatives for reducing breast cancer incidence and mortality.
Tumor cells, including cancer stem cells (CSCs) resistant to radio- and chemotherapy, must enhance metabolism to meet the extra energy demands to repair and survive such genotoxic conditions. ...However, such stress-induced adaptive metabolic alterations, especially in cancer cells that survive radiotherapy, remain unresolved. In this study, we found that CPT1 (Carnitine palmitoyl transferase I) and CPT2 (Carnitine palmitoyl transferase II), a pair of rate-limiting enzymes for mitochondrial fatty acid transportation, play a critical role in increasing fatty acid oxidation (FAO) required for the cellular fuel demands in radioresistant breast cancer cells (RBCs) and radiation-derived breast cancer stem cells (RD-BCSCs). Enhanced CPT1A/CPT2 expression was detected in the recurrent human breast cancers and associated with a worse prognosis in breast cancer patients. Blocking FAO via a FAO inhibitor or by CRISPR-mediated CPT1A/CPT2 gene deficiency inhibited radiation-induced ERK activation and aggressive growth and radioresistance of RBCs and RD-BCSCs. These results revealed that switching to FAO contributes to radiation-induced mitochondrial energy metabolism, and CPT1A/CPT2 is a potential metabolic target in cancer radiotherapy.
Opinion statement
It has become clear that patients whose cancers have progressed post-CDK4/6 inhibitor therapy (CDK4/6i) are not deriving the same magnitude of benefit to subsequent standard ...endocrine therapy as historical studies would suggest. For example, anticipated duration of benefit to fulvestrant prior to CDK4/6i historically was ~ 5–6 months, and data from the VERONICA and EMERALD trials report less than 2 months. This has magnified our need for novel endocrine agents. Some have argued that patients post-CDK4/6i may just have more endocrine-resistant tumors and perhaps should just receive chemotherapy. While this may be appropriate for some, we do not currently have an assay that reliably predicts whose cancers remain endocrine sensitive and whose are endocrine resistant. ESR1 mutations can enrich for patients whose tumors are more likely to be heavily dependent on estrogen, but this is certainly not the whole answer and many patients without ESR1 mutations continue to derive benefit from subsequent endocrine agents. Most patients would strongly prefer the side effect profile of endocrine agents compared to chemotherapy, and thus, premature use of cytotoxic agents when subsequent ER targeting can control disease is not preferred. These novel ER targeting agents (PROTAC, SERD, SERCA, CERAN) hold great promise to not only outperform standard agents like fulvestrant, but also offer the promise of agents with a different side effect profile that may be more advantageous when compared to menopausal symptoms, hot flashes, arthralgias, and sexual side effects so commonly seen with AIs. We also are likely to see these novel agents move to earlier lines, whether that be 1st line in combination with CDK4/6i or even adjuvant disease.
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