Breast cancer is uncommon in young women and correlates with a less favourable prognosis; still it is the most frequent cancer in women under 40, accounting for 30-40% of all incident female cancer. ...The aim of this study was to study prognosis in young women, quantifying how much stage at diagnosis and management on the one hand, and tumour biology on the other; each contribute to the worse prognosis seen in this age group.
In a registry based cohort of women aged 20-69 (n = 22 017) with a primary diagnosis of invasive breast cancer (1992-2005), women aged 20-34 (n = 471), 35-39 (n = 858) and 40-49 (n = 4789) were compared with women aged 50-69 years (n = 15 899). The cumulative 5-year relative survival ratio and the relative excess mortality (RER) were calculated. The cumulative 5-year relative survival ratio was lowest in women aged 20-34. The RER was 2.84 for women aged 20-34 and decreased with increasing age (RER 1.76 and 1.17 for women aged 35-39 and 40-49, respectively). The excess risk was, however, present only in disease stages I and II. For women aged 20-34 with stage I disease RER was 4.63, and 6.70 in the subgroup with tumour size 1-10 mm. The absolute difference in stage I between the youngest and the reference groups amounted to nearly 8%, with a 90% 5-year survival in women aged 20-34. In stages IIa and IIb, the relative excess risk was not as dramatic, but the absolute differences approached 15%. The youngest women with small tumours generally received more aggressive treatment than women in older age groups.
After correction for stage, tumour characteristics and treatment, age remained an independent risk factor for breast cancer death in women <35 years of age. The excess risk for young women was only seen in early stages of disease and was most pronounced in women with small tumours. Young women affected by breast cancer have a high risk of dying compared to their middle-aged counterparts even if diagnosed early and receiving an intense treatment.
The role of axillary lymph node dissection (ALND) has increasingly been called into question among patients with positive sentinel lymph nodes. Two recent trials have failed to show a survival ...difference in sentinel node-positive breast cancer patients who were randomized either to undergo completion ALND or not. Neither of the trials, however, included breast cancer patients undergoing mastectomy or those with tumors larger than 5 cm, and power was debatable to show a small survival difference.
The prospective randomized SENOMAC trial includes clinically node-negative breast cancer patients with up to two macrometastases in their sentinel lymph node biopsy. Patients with T1-T3 tumors are eligible as well as patients prior to systemic neoadjuvant therapy. Both breast-conserving surgery and mastectomy, with or without breast reconstruction, are eligible interventions. Patients are randomized 1:1 to either undergo completion ALND or not by a web-based randomization tool. This trial is designed as a non-inferiority study with breast cancer-specific survival at 5 years as the primary endpoint. Target accrual is 3500 patients to achieve 80% power in being able to detect a potential 2.5% deterioration of the breast cancer-specific 5-year survival rate. Follow-up is by annual clinical examination and mammography during 5 years, and additional controls after 10 and 15 years. Secondary endpoints such as arm morbidity and health-related quality of life are measured by questionnaires at 1, 3 and 5 years.
Several large subgroups of breast cancer patients, such as patients undergoing mastectomy or those with larger tumors, have not been included in key trials; however, the use of ALND is being questioned even in these groups without the support of high-quality evidence. Therefore, the SENOMAC Trial will investigate the need of completion ALND in case of limited spread to the sentinel lymph nodes not only in patients undergoing any breast surgery, but also in neoadjuvantly treated patients and patients with larger tumors.
NCT 02240472 , retrospective registration date September 14, 2015 after trial initiation on January 31, 2015.
Breast cancer is a leading cause of death among women worldwide. Increasing evidence implies that human cytomegalovirus (HCMV) infection is associated with several malignancies. We aimed to examine ...whether HCMV is present in breast cancer and sentinel lymph node (SLN) metastases.
Formalin-fixed paraffin-embedded tissue specimens from breast cancer and paired sentinel lymph node (SLN) samples were obtained from patients with (n = 35) and without SLN metastasis (n = 38). HCMV immediate early (IE) and late (LA) proteins were detected using a sensitive immunohistochemistry (IHC) technique and HCMV DNA by real-time PCR.
HCMV IE and LA proteins were abundantly expressed in 100% of breast cancer specimens. In SLN specimens, 94% of samples with metastases (n = 34) were positive for HCMV IE and LA proteins, mostly confined to neoplastic cells while some inflammatory cells were HCMV positive in 60% of lymph nodes without metastases (n = 35). The presence of HCMV DNA was confirmed in 12/12 (100%) of breast cancer and 10/11 (91%) SLN specimens from the metastatic group, but was not detected in 5/5 HCMV-negative, SLN-negative specimens. There was no statistically significant association between HCMV infection grades and progesterone receptor, estrogen receptor alpha and Elston grade status.
The role of HCMV in the pathogenesis of breast cancer is unclear. As HCMV proteins were mainly confined to neoplastic cells in primary breast cancer and SLN samples, our observations raise the question whether HCMV contributes to the tumorigenesis of breast cancer and its metastases.
This report evaluates whether health related quality of life (HRQoL) and patient-reported arm morbidity one year after axillary surgery are affected by the omission of axillary lymph node dissection ...(ALND).
The ongoing international non-inferiority SENOMAC trial randomizes clinically node-negative breast cancer patients (T1-T3) with 1–2 sentinel lymph node (SLN) macrometastases to completion ALND or no further axillary surgery. For this analysis, the first 1181 patients enrolled in Sweden and Denmark between March 2015, and June 2019, were eligible. Data extraction from the trial database was on November 2020. This report covers the secondary outcomes of the SENOMAC trial: HRQoL and patient-reported arm morbidity. The EORTC QLQ-C30, EORTC QLQ-BR23 and Lymph-ICF questionnaires were completed in the early postoperative phase and at one-year follow-up. Adjusted one-year mean scores and mean differences between the groups are presented corrected for multiple testing.
Overall, 976 questionnaires (501 in the SLN biopsy only group and 475 in the completion ALND group) were analysed, corresponding to a response rate of 82.6%. No significant group differences in overall HRQoL were identified. Participants receiving SLN biopsy only, reported significantly lower symptom scores on the EORTC subscales of pain, arm symptoms and breast symptoms. The Lymph-ICF domain scores of physical function, mental function and mobility activities were significantly in favour of the SLN biopsy only group.
One year after surgery, arm morbidity is significantly worse affected by ALND than by SLN biopsy only. The results underline the importance of ongoing attempts to safely de-escalate axillary surgery.
The trial was registered at clinicaltrials.gov prior to initiation (https://clinicaltrials.gov/ct2/show/NCT 02240472).
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•Omission of ALND significantly reduces patient-reported arm morbidity.•SLNB versus ALND results in significant less pain and better physical function.•HRQoL is not affected by de-escalated axillary surgery.•Complaints from axillary surgery are evaluated with patient-reported outcomes.
The aim of this study was to determine the prognostic significance of lymph node micrometastases in patients with breast cancer.
Between September 2000 and January 2004, 3,369 patients with breast ...cancer were included in a prospective cohort. According to their lymph node status, they were classified in the following four groups: 2,383 were node negative, 107 had isolated tumor cells, 123 had micrometastases, and 756 had macrometastases. Median follow-up time was 52 months. Kaplan-Meier estimates and the multivariate Cox proportional hazard regression model were used to analyze survival.
Five-year cause-specific and event-free survival rates were lower for patients with micrometastases (pN1mi) than for node-negative (pN0) patients (94.1% v 96.9% and 79.6% v 87.1%, respectively; P = .020 and P = .032, respectively). There was no significant survival difference between node-negative patients and those with isolated tumor cells. The overall survival of pN1mi and pN0 patients did not differ.
This study demonstrates a worse prognosis for patients with micrometastases than for node-negative patients.
Transcriptomic profiling of breast tumors provides opportunity for subtyping and molecular-based patient stratification. In diagnostic applications the specimen profiled should be representative of ...the expression profile of the whole tumor and ideally capture properties of the most aggressive part of the tumor. However, breast cancers commonly exhibit intra-tumor heterogeneity at molecular, genomic and in phenotypic level, which can arise during tumor evolution. Currently it is not established to what extent a random sampling approach may influence molecular breast cancer diagnostics.
In this study we applied RNA-sequencing to quantify gene expression in 43 pieces (2-5 pieces per tumor) from 12 breast tumors (Cohort 1). We determined molecular subtype and transcriptomic grade for all tumor pieces and analysed to what extent pieces originating from the same tumors are concordant or discordant with each other. Additionally, we validated our finding in an independent cohort consisting of 19 pieces (2-6 pieces per tumor) from 6 breast tumors (Cohort 2) profiled using microarray technique. Exome sequencing was also performed on this cohort, to investigate the extent of intra-tumor genomic heterogeneity versus the intra-tumor molecular subtype classifications.
Molecular subtyping was consistent in 11 out of 12 tumors and transcriptomic grade assignments were consistent in 11 out of 12 tumors as well. Molecular subtype predictions revealed consistent subtypes in four out of six patients in this cohort 2. Interestingly, we observed extensive intra-tumor genomic heterogeneity in these tumor pieces but not in their molecular subtype classifications.
Our results suggest that macroscopic intra-tumoral transcriptomic heterogeneity is limited and unlikely to have an impact on molecular diagnostics for most patients.
To evaluate clinical outcomes of using acellular dermal matrix (ADM) with implant based breast reconstructions (IBBRs) in a randomized controlled trial.
The use of ADMs in IBBRs is widespread, but ...link between ADM and complications remain a controversial topic. In view of reports concerning harm, we present 6-months safety data of ADM-assisted IBBR in the setting of breast cancer treatment.
An open-label, randomized, controlled trial recruiting patients from 4 centers in Sweden and 1 in UK. Eligible were women with breast cancer planned for mastectomy with immediate IBBR. Participants were randomly allocated to IBBR with or without ADM (Strattice, Branchburg, NJ), with stratification by center in blocks of 6. Main primary endpoint was number of unplanned reoperations at 24 months, and safety expressed as the incidence of adverse events with a 6-month follow-up time for all participants. Analysis were done per protocol using Fisher exact test for complications and reoperations.
From start of enrolment on April 24, 2014, to close of trial on May 10, 2017, 135 women were enrolled, of whom 64 with ADM and 65 without ADM were included in the final analysis. Four patients (6%) in each group had reconstructive failure with implant loss, but IBBR with ADM exhibited a trend of more overall complications and reoperations (difference 0·16, 95% CI, -0·01 to 0·32, P = 0·070), and with higher risk of wound healing problems (P = 0·013).
With 6-months follow-up for all participants, immediate IBBR with ADM carried a risk of implant loss equal to conventional IBBR without ADM, but was associated with more adverse outcomes requiring surgical intervention. Further investigation of risk factors and patient selection in a long-term follow-up is warranted.
Results from several randomised mammography screening trials have shown that it is possible to reduce mortality in breast cancer by mammographic screening at least for women above 50 years of age. ...The purpose of this article is to present data on mortality in breast cancer in study and control groups of the Stockholm trial after 11 years of followup, to analyse which age group benefits most from screening. In March 1981, 40,318 women in Stockholm, aged 40 through 64 years, entered a randomized trial of breast cancer screening by single view mammography alone, versus no intervention in a control group of 20,000 women. Two screening rounds were performed and the attendance rate was over 80% in the two rounds. During 1986 the control group was invited once to screening. Totally 428 and 217 cases of breast cancer were diagnosed in the study and control groups respectively. After a mean follow-up of 11.4 years a nonsignificant mortality reduction of 26% was observed for the whole study group, with a relative risk (RR) of death in breast cancer of 0.74 (CI(confidence interval) = 0.5-1.1). For women aged 50-64 years a significant 38% mortality reduction was observed with a RR of 0.62 (CI = 0.38-1.0). For women aged 40-49 years no effect on mortality was found, with a RR of death in breast cancer of 1.08 (CI = 0.54-2.17). The breakpoint for benefit in this study seemed to be at 50 years of age when 5-year age groups were analysed, but this tendency is uncertain because of the low statistical power in the analysis of the younger age groups. Long screening intervals, the use of single-view mammography, and the fact that more than 50% of the women in age group 40-49 years were still below 50 years of age when the study was closed, were all facts that could have influenced the results in age group 40-49 years. Larger studies are needed to answer the question whether mammographic screening can be successful in younger age groups.
Current evidence for the effects of radiotherapy (RT) on implant-based immediate breast reconstruction (IBR) is limited by short follow-up and lack of patient-reported outcomes (PROs). It is central ...to integrate long-term comprehensive outcome data into the preoperative decision-making process. The aim of the present study was to determine long-term surgical outcomes and PROs in relation to RT after implant-based IBR.
This was a longitudinal cohort study of PRO data obtained in surveys conducted in 2012 and 2020 using the BREAST-Q questionnaire. All women undergoing therapeutic mastectomy and implant-based IBR between 1 January 2007 and 31 December 2011 at four breast centres in Stockholm, Sweden, were identified. The endpoint was implant removal owing to surgical complications or patient preference.
Median follow-up was 120 (range 1-171) months. After 754 IBRs in 729 women, implant removal occurred in 128 (17 per cent): 34 of 386 (8.8 per cent) in the no-RT group, 20 of 64 (31.3 per cent) in the group with previous RT, and 74 of 304 (24.3 per cent) in the postoperative RT group (P < 0.001). Implant removal was because of surgical complications in 60 instances (7.9 per cent), and patient preference in 68 (9.0 per cent). The BREAST-Q response rate was 72.2 per cent. Women with previous RT scored lower than those without RT on all scales, apart from psychosocial well-being. Women with postoperative RT scored lower only on physical well-being. No scores in the two RT groups had deteriorated between the survey time points, whereas satisfaction with breasts and overall outcome had decreased in the no-RT group.
Although RT was significantly associated with higher implant removal rates, PROs remained stable over 8 years despite irradiation.
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