Purpose
To determine the biology, recurrence rate, metastatic patterns and survival times in primary triple-negative breast cancer (TNBC) with focus on the comparison between younger and elderly ...patients.
Methods
Patients with primary TNBC stage I–IV diagnosed from 2007 to 2015 were identified and information on tumor biology, stage, treatment, recurrences and death recorded.
Results
A total of 524 patients, median age 60 years (range 24–94) with a median follow-up of 55 months (range 0–129) were identified. Stage was similar in younger (< 40 years) (
n
= 58) and older (> 74 years) (
n
= 96) patients (
p
= 0.37). A statistically significant difference was found concerning histopathologic grade (
p
= 0.006) and Ki67 (median 80% versus 70%;
p
= 0.002) but not for LVI (
p
= 0.9) with more aggressive tumors among younger patients. Adjuvant/neoadjuvant chemotherapy was more frequently given to younger compared with older patients (96% versus 12%;
p
= 0.0005). Only brain (
p
= 0.016) and liver (
p
= 0.047) metastases were more often registered among younger patients while other locations were similar. Shorter survival times, recurrence-free survival (RFS), distant disease-free survival (DDFS) and breast cancer-specific survival (BCSS) were found in the older group, although not after adjusting for adjuvant/neoadjuvant chemotherapy. Most deaths (68%) in the older group were caused by TNBC. When comparing patients > 75 years (
n
= 92) with ≤ 75 years (
n
= 432), a worse outcome among older was also observed: RFS (
p
= 0.00012), DDFS (
p
= 0.00041), BCSS (
p
< 0.0001) and survival following distant metastasis (
p
= 0.0064)
Conclusions
Primary TNBC in younger patients is more often of poor differentiation grade and highly proliferative compared with older patients. The majority of older patients still have grade III tumors with a Ki67 > 60% and outcome is poor. Few older patients in our study were treated with chemotherapy both in adjuvant and palliative setting, underlining the need for more prospective trials and treatment options suitable for this patient population.
De Novo Oligometastatic Breast Cancer Pusztai, Lajos; Rozenblit, Mariya; Dubsky, Peter ...
Journal of clinical oncology,
12/2023, Letnik:
41, Številka:
34
Journal Article
Triple-negative breast cancer (TNBC) lacking expression of steroid receptors and human epidermal growth factor receptor 2, having chemotherapy as the only therapeutic option, is characterised by ...early relapses and poor outcome. We investigated intratumoural (i.t.) levels of the pro-angiogenic cytokine vascular endothelial growth factor (VEGF) and survival in patients with TNBC compared with non-TNBC.
VEGF levels were determined by an enzyme immunosorbent assay in a retrospective series consisting of 679 consecutive primary breast cancer patients.
Eighty-seven patients (13%) were classified as TNBC and had significantly higher VEGF levels; median value in TNBC was 8.2 pg/μg DNA compared with 2.7 pg/μg DNA in non-TNBC (P<0.001). Patients with TNBC had statistically significant shorter recurrence-free survival hazard ratio (HR)=1.8; P=0.0023, breast cancer-corrected survival (HR=2.2; P=0.004) and overall survival (HR=1.8; P=0.005) compared with non-TNBC. Patients with TNBC relapsed earlier than non-TNBC; mean time from diagnosis to first relapse was 18.8 and 30.7 months, respectively. The time between first relapse and death was also shorter in TNBC: 7.5 months versus 17.5 months in non-TNBC (P=0.087).
Our results show that TNBC have higher i.t. VEGF levels compared with non-TNBC. Ongoing clinical trials will answer if therapy directed towards angiogenesis may be an alternative way to improve outcome in this poor prognosis group.
There is limited knowledge of the biology of breast cancer (BC) brain metastasis (BM). We primarily aimed to determine the mutations in BCBM and to compare the mutational pattern with the matched ...primary breast cancer (BC). Secondary aims were to determine mutations in each subgroup (Luminal A-/B-like, HER2+ and TNBC) of BCBM, and to determine survival according to specific mutations. We investigated 57 BCBMs, including 46 cases with matched primary tumors (PT) by targeted Next Generation Sequencing (NGS) using the Cancer Hotspot Panel v2 (ThermoFisher Scientific) covering 207 targeted regions in 50 cancer related genes. Subtype according to immunohistochemistry was re-evaluated. NGS results fulfilling sequencing quality criteria were obtained from 52 BM and 41 PT, out of which 37 were matched pairs. Pathogenic mutations were detected in 66% of PTs (27/41), and 62% of BMs (32/52). TP53 mutations were most frequent; 49% (20/41) of PTs and 48% (25/52) in BMs, followed by PIK3CA mutations; 22% (9/42) in PTs and 25% (13/52) in BMs. Mutations in CDH1, EGFR, HRAS, RB1 CDKN2A and PTEN were detected in single pairs or single samples. Mutational pattern was discordant in 24% of matched pairs. We show a discordance of PIK3CA and TP53 mutations of roughly 25% indicating the need to develop methods to assess mutational status in brain metastasis where analysis of cell-free DNA from cerebrospinal fluid (CSF) has shown promising results.
Cancer is a growing concern in Ethiopia. Though communication is essential for the treatment process, few studies have looked at communication in Ethiopian cancer care. Due to the large number of ...patients and scarcity of resources, it is vital to understand how to manage consultations in order to effectively help as many patients as possible in this challenging work environment. Thus, research is needed to analyze and understand the communicative challenges experienced by physicians, patients, and family caregivers, in order to successfully handle patient care in practice.
We explore communication in Ethiopian cancer care and present the main challenges faced by physicians, patients, and family caregivers.
This explorative qualitative study was conducted at the Oncology Department of the Tikur Anbessa (Black Lion) Specialized Teaching Hospital (TASH) in Addis Ababa, Ethiopia. A triangulation of data collection methods was used: 91 audio-recorded, semi-structured interviews and 21 video-recordings of authentic interactions during hospital rounds. The aim was to obtain as complete a picture as possible of communication from the perspectives of physicians, patients, and family caregivers. The interviews were analyzed using thematic content analysis and the identified themes were supported by excerpts from the transcribed recordings.
Eight themes emerged from the data. Workload and time pressure, in combination with restricted space for privacy, limited the possibilities for physicians to deliver detailed information and provide emotional support. Furthermore, patient literacy levels, in combination with no or little cancer awareness, financial problems, reliance on traditional and religious treatments, the stigma of cancer, and a fatalistic attitude, resulted in delays in patients seeking care and participating in positive health behaviors, and, subsequently, often resulted in an unwillingness to openly discuss problems with physicians and adhere to treatment. The study also illustrates the paramount role of family in physician-patient communication in Ethiopia. Though family caregivers provide a valuable interpreting support when patients have limited language skills, they can also prevent patients from sharing information with physicians. Another important finding is that family caregivers were often responsible for making decisions about treatment and avoided telling patients about a poor prognosis, believing that conveying bad news may upset them. All of these themes have important implications for the role of ethically acceptable communication in patient-centered care.
This study has identified a number of serious challenges for successful and ethically acceptable health communication in Ethiopian cancer care. The study contributes to our understanding of the complexity around the role of family, combined with patients' dependency on family members for communication, support, and access to care, which creates particular ethical dilemmas for the medical staff. The questions raised by this study concern how to organize consultations to achieve patient-centered health communication, while maintaining a constructive alliance with the family and not jeopardizing the patient's continued access to care. The integration of communication training for medical students in Ethiopia, with a focus on ethical guidelines for family-centered patient consultation suitable for these circumstances, would be an essential step.
To evaluate the benefit of low-dose cyclophosphamide and methotrexate (CM) maintenance, which previously demonstrated antitumor activity and few adverse effects in advanced breast cancer, in early ...breast cancer.
International Breast Cancer Study Group (IBCSG) Trial 22-00, a randomized phase III clinical trial, enrolled 1,086 women (1,081 intent-to-treat) from November 2000 to December 2012. Women with estrogen receptor- and progesterone receptor-negative (< 10% positive cells by immunohistochemistry) early breast cancer any nodal and human epidermal growth factor receptor 2 status, were randomly assigned anytime between primary surgery and 56 days after the first day of last course of adjuvant chemotherapy to CM maintenance (cyclophosphamide 50 mg/day orally continuously and methotrexate 2.5 mg twice/day orally on days 1 and 2 of every week for 1 year) or to no CM. The primary end point was disease-free survival (DFS), which included invasive recurrences, second (breast and nonbreast) malignancies, and deaths.
After a median of 6.9 years of follow-up, DFS was not significantly better for patients assigned to CM maintenance compared with patients assigned to no CM, both overall (hazard ratio HR, 0.84; 95% CI, 0.66 to 1.06;P = .14) and in triple-negative (TN) disease (n = 814; HR, 0.80; 95% CI, 0.60 to 1.06). Patients with TN, node-positive disease had a nonstatistically significant reduced HR (n = 340; HR, 0.72; 95% CI, 0.49 to 1.05). Seventy-one (13%) of 542 patients assigned to CM maintenance did not start CM. Of 473 patients who received at least one CM maintenance dose (including two patients assigned to no CM), 64 (14%) experienced a grade 3 or 4 treatment-related adverse event; elevated serum transaminases was the most frequently reported (7%), followed by leukopenia (2%).
CM maintenance did not produce a significant reduction in DFS events in hormone receptor-negative early breast cancer. The trend toward benefit observed in the TN, node-positive subgroup supports additional exploration of this strategy in the TN, higher-risk population.
About one-third of oestrogen receptor alpha-positive breast cancer patients treated with tamoxifen relapse. Here we identify the nuclear receptor retinoic acid receptor alpha as a marker of tamoxifen ...resistance. Using quantitative mass spectrometry-based proteomics, we show that retinoic acid receptor alpha protein networks and levels differ in a tamoxifen-sensitive (MCF7) and a tamoxifen-resistant (LCC2) cell line. High intratumoural retinoic acid receptor alpha protein levels also correlate with reduced relapse-free survival in oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen solely. A similar retinoic acid receptor alpha expression pattern is seen in a comparable independent patient cohort. An oestrogen receptor alpha and retinoic acid receptor alpha ligand screening reveals that tamoxifen-resistant LCC2 cells have increased sensitivity to retinoic acid receptor alpha ligands and are less sensitive to oestrogen receptor alpha ligands compared with MCF7 cells. Our data indicate that retinoic acid receptor alpha may be a novel therapeutic target and a predictive factor for oestrogen receptor alpha-positive breast cancer patients treated with adjuvant tamoxifen.
Clinical outcome of patients with triple-negative breast cancer (TNBC) is highly variable. This study aims to identify and validate a prognostic protein signature for TNBC patients to reduce ...unnecessary adjuvant systemic therapy.
Frozen primary tumors were collected from 126 lymph node-negative and adjuvant therapy-naive TNBC patients. These samples were used for global proteome profiling in two series: an in-house training (n = 63) and a multicenter test (n = 63) set. Patients who remained free of distant metastasis for a minimum of 5 years after surgery were defined as having good prognosis. Cox regression analysis was performed to develop a prognostic signature, which was independently validated. All statistical tests were two-sided.
An 11-protein signature was developed in the training set (median follow-up for good-prognosis patients = 117 months) and subsequently validated in the test set (median follow-up for good-prognosis patients = 108 months) showing 89.5% sensitivity (95% confidence interval CI = 69.2% to 98.1%), 70.5% specificity (95% CI = 61.7% to 74.2%), 56.7% positive predictive value (95% CI = 43.8% to 62.1%), and 93.9% negative predictive value (95% CI = 82.3% to 98.9%) for poor-prognosis patients. The predicted poor-prognosis patients had higher risk to develop distant metastasis than the predicted good-prognosis patients in univariate (hazard ratio HR = 13.15; 95% CI = 3.03 to 57.07; P = .001) and multivariable (HR = 12.45; 95% CI = 2.67 to 58.11; P = .001) analysis. Furthermore, the predicted poor-prognosis group had statistically significantly more breast cancer-specific mortality. Using our signature as guidance, more than 60% of patients would have been exempted from unnecessary adjuvant chemotherapy compared with conventional prognostic guidelines.
We report the first validated proteomic signature to assess the natural course of clinical TNBC.
•This study presents real world data on compliance to endocrine therapy in Swedish breast cancer patients.•Statistically significant reduction of recurrences and death due to breast cancer thanks to ...compliance to endocrine treatment after 20 years of follow up.•Extracting data from patients’ records gives real world perspective of prevalence of treatment discontinuation.
Data on compliance to adjuvant endocrine treatment (ET) is mainly reported from prospective clinical trials or from smaller retrospective cohorts without correlation to outcome.
To determine compliance to adjuvant ET and the impact on survival in a population-based series of patients with early breast cancer (BC) advised ET.
1090 consecutive patients with hormone receptor positive (HR+) stage I-III BC diagnosed from 1 January 1997 to 31 December 2003 from one health care region of Sweden were included. Data on tumour, type of ET, compliance, reason for termination and outcome were collected. Statistical analyses were calculated with patients in three groups.
72 patients were excluded leaving 1018 patients with a HR+ stage I to III BC for analyses. The most common ET was tamoxifen (n = 751, 73.8%). At the last follow up (31 Dec 2019) with a median follow-up of 18 years (interquartile range 16–22) 228 (22.4%) patients had a relapse. 71.1% of the included patients were compliant to endocrine therapy. Older patients ≥74 years had lower compliance, 61% compared with 75% in the other age groups (≤50 years and 51–73 years) (p < 0001), other parameters including type of ET were not associated with compliance. Low compliance remained as an independent risk factor in multivariate analyses for lower relapse-free survival, HR=1.83, 95% Confidence Interval (CI) 1.52–2.19, p < 0.001 and for time to BC death, HR=2.69, 95%CI 1.82–3.98, p < 0.001.
Patients compliant to adjuvant ET have an improved survival.
•Overall survival appears inferior among men with breast cancer compared to women.•Differences are found on DNA and RNA levels between male and female breast cancers.•Two subgroups of male breast ...cancer were identified based on global mRNA/DNA data.•The male breast cancer subgroups differ from the subtypes of female breast cancer.•Aggressive male breast cancers may have an inactive ER pathway despite ER positivity.
Breast cancer is the most common cancer form in women and it has been extensively studied on the molecular level. Male breast cancer (MBC), on the other hand, is rare and has not been thoroughly investigated in terms of transcriptional profiles or genomic aberrations. Most of our understanding of MBC has therefore been extrapolated from knowledge of female breast cancer. Although differences in addition to similarities with female breast cancer have been reported, the same prognostic and predictive markers are used to determine optimal management strategies for both men and women diagnosed with breast cancer. This review is focused on prognosis for MBC patients, prognostic and predictive factors and molecular subgrouping; comparisons are made with female breast cancer. Information was collected from relevant literature on both male and female breast cancer from the MEDLINE database between 1992 and 2014.
MBC is a heterogeneous disease, and on the molecular level many differences compared to female breast cancer have recently been revealed. Two distinct subgroups of MBC, luminal M1 and luminal M2, have been identified which differ from the well-established intrinsic subtypes of breast cancer in women. These novel subgroups of breast cancer therefore appear unique to MBC. Furthermore, several studies report inferior survival for men diagnosed with breast cancer compared to women. New promising prognostic biomarkers for MBC (e.g. NAT1) deserving further attention are reviewed. Further prospective studies aimed at validating the novel subgroups and recently proposed biomarkers for MBC are warranted to provide the basis for optimal patient management in this era of personalized medicine.
This article is part of a Directed Issue entitled: Rare Cancers.
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