Impact of schizophrenia and related disorders on mortality from breast cancer: A population-based cohort study in Denmark, 1995–2011

ObjectivesTo investigate overall and breast cancer-specific mortality in early-stage breast cancer patients with and without schizophrenia or related disorders.MethodsWe used Danish national registers to identify all women with no prior history of cancer or organic mental disorders, who were diagnosed with early-stage breast cancer 1995–2011. Logistic regression models were used to calculate the odds ratios (ORs) for not being allocated to guideline treatment. Cox regression models were used to compute hazard ratios (HRs) for overall and breast cancer-specific deaths among women allocated or not allocated to guideline treatment.ResultsWe identified 56,152 women with early-stage breast cancer diagnosed in 1995–2011, of whom 499 women also had been diagnosed with schizophrenia or related disorders. The likelihood of women with schizophrenia or related disorders for not being allocated to guideline treatment was increased (adjusted OR, 1.50; 95% confidence interval (CI), 1.15–1.94). The adjusted HR for all-cause mortality was 1.55; 95% CI, 1.32–1.82 and 1.12 (95% CI, 0.98–1.50) for breast cancer-specific mortality; women allocated to guideline treatment had an adjusted HR for breast cancer-specific death of 1.42 (95% CI, 1.11–1.82). The adjusted HR for death due to unnatural causes was 3.67 (95% CI, 1.80–7.35).ConclusionThe survival of women with schizophrenia or related disorders after breast cancer is significantly worse than that of women without these disorders. These patients are less likely to be allocated to guideline treatment, and, among those who are, mortality from both breast cancer and other causes is increased.     

Obstetric complications at time of delivery amongst breast cancer survivors: A population-based cohort study

PurposeOur aim was to determine whether breast cancer survivors are at increased risk of obstetric and maternal complications at time of delivery.MethodsThe USA ‘National Inpatient Sample’ database was queried for hospitalizations associated with deliveries, between 2015 and 2018. The incidence of maternal and fetal complications was compared between women with, and without, a personal history of breast cancer.ResultsOf the 2,103,216 birth related admissions, 617 (0.03%) of the women were breast cancer survivors, with the proportion increasing over time (from 0.02% in 2015 to 0.04% in 2018). Breast cancer survivors had a higher socioeconomic status (p < 0.001) and were significantly older compared to other mothers (34 vs. 28 years, p < 0.001). Additionally, they were more likely to suffer from preexisting chronic diseases including cardiopulmonary disease and diabetes mellitus, and had a higher incidence of multiple gestation (4.4% vs. 1.6%) [OR 2.7, 95% CI 1.9–4.0, p < 0.001]. The incidence of acute adverse events at time of delivery including fetal distress, preterm labor, cesarean section and maternal infection was higher amongst the breast cancer survivors. On multivariate analysis age, ethnic group, comorbidities, multiple gestations, and a previous breast cancer diagnosis, but not cancer treatment, were associated with an increased risk of an obstetric adverse event.ConclusionBreast cancer survivors have more comorbidities and are at increased risk of acute obstetrical complications at time of delivery. Further studies are required to validate these findings, and evaluate the ability of interventions to improve obstetrical outcomes amongst breast cancer survivors.     

The impact of patient characteristics and lifestyle factors on the risk of an ipsilateral event after a primary DCIS: A systematic review

ObjectiveThe majority of ‘low-risk’ (grade I/II) Ductal Carcinoma In Situ (DCIS) may not progress to invasive breast cancer during a women’s lifetime. Therefore, the safety of active surveillance versus standard surgical treatment for DCIS is prospectively being evaluated in clinical trials. If proven safe and selectively implemented in clinical practice, a significant group of women with low-risk DCIS may forego surgery and radiotherapy in the future. Identification of modifiable and non-modifiable risk factors associated with prognosis after a primary DCIS would also enhance our care of women with low-risk DCIS.MethodsTo identify modifiable and non-modifiable risk factors for subsequent breast events after DCIS, we performed a systematic literature search in PUBMED, EMBASE and Scopus.ResultsSix out of the 3870 articles retrieved were included for final data extraction. These six studies included a total of 4950 patients with primary DCIS and 640 recorded subsequent breast events. There was moderate evidence for an association of a family history of breast cancer, premenopausal status, high BMI, and high breast density with a subsequent breast cancer or further DCIS.ConclusionThere is a limited number of recent studies published on the impact of modifiable and non-modifiable risk factors on subsequent events after DCIS. The available evidence is insufficient to identify potential targets for risk reduction strategies, reflecting the relatively small numbers and the lack of long-term follow-up in DCIS, a low-event condition.     

Effects of tamoxifen and aromatase inhibitors on the risk of acute coronary syndrome in elderly breast cancer patients: An analysis of nationwide data

BackgroundAromatase inhibitors (AIs) are the preferred endocrine treatment for postmenopausal hormonal receptor-positive breast cancer. However, there is controversy on the long-term cardiovascular and cerebrovascular safety of AIs over that of tamoxifen.MethodsWe analyzed the National Health Information Database (NHID) of 281,255 women over a 20-year-old diagnosed with breast cancer between 2009 and 2016. Cardiovascular events (CVEs) were defined as the development of the following, acute coronary syndrome (ACS), ischemic and hemorrhagic stroke, defined by using insurance claim records. The model was constructed by Cox proportional hazard regression and this model was used to analyze the effects of AI and tamoxifen on CVE.ResultsWe included 47,569 women for the final analysis. Patients were classified into ‘No hormonal treatment (n = 18,807), ‘Switch (n = 2097)’, ‘Tamoxifen (n = 7081)’ and ‘AI (n = 19,584)’. There were 2147 CVEs in 2032 patients (4.1%). Univariate analysis showed that women with tamoxifen had significantly lower risk for CVEs compared to no-treatment (hazard ratio (HR) 0.84, 95% confidence interval (CI) 0.74–0.97) while AI showed no such effect (HR 0.93, 95% CI 0.84–1.02). After adjusting for other risk factors (hypertension, dyslipidemia, family history), the use of tamoxifen was associated with significant protective effect against ACS (HR 0.63, 95% CI 0.47–0.84).ConclusionsOur results, based on the NHID, supports the protective effect of tamoxifen against CVE in Korean breast cancer patients aged 55 and older that is not seen with AIs. Our results can guide the selection of adjuvant hormonal treatment agents for Korean breast cancer patients based on their risk of developing CVE.     

Moderately hypofractionated post-operative radiation therapy for breast cancer: Systematic review and meta-analysis of randomized clinical trials

IntroductionWe provide a critical assessment regarding current evidence for the use of moderately hypofractionated irradiation for patients with breast cancer. The aim of the study was to summarize the available evidence regarding outcomes after moderately hypofractionated compared with conventional radiation doses in the post-operative treatment of patients with breast cancer.Material and methodsThe Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE and LILACS databases were searched until March 25, 2021. All randomized phase 3 clinical trials that compared moderately hypofractionated with conventional radiation doses in the post-operative treatment of patients with breast cancer were selected. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement.ResultsEight clinical trials satisfied the eligibility criteria and were the focus of the analysis. A total of 12,139 breast cancer patients was randomly assigned for moderately hypofractionated compared with conventional irradiation. Meta-analysis of the trials regarding local recurrence, loco-regional recurrence, disease-free survival, and overall survival outcomes did not demonstrate any significant difference between moderately hypofractionated irradiation and conventional radiation doses groups. The rate of severe side effects was low in both groups; acute and late side effects and cosmesis were similar or even tended to be lower after moderately hypofractionated than after conventional irradiation.ConclusionsModerately hypofractionated is at least as effective and safe as conventional radiation irradiation regimens and should be considered as a treatment option for most, if not all, breast cancer patients.     

T-DM1 and brain metastases: Clinical outcome in HER2-positive metastatic breast cancer

BackgroundWe reported the results of an Italian large retrospective analysis that evaluated the effectiveness and safety of T-DM1 in ‘field-practice’ breast cancer patients. We performed a sub-analysis to investigate the clinical activity of T-DM1 in patients with brain metastases (BMs).MethodsThe records of 87 adult women with HER2-positive breast cancer and BMs treated with T-DM1 were reviewed. Their clinical outcomes were compared with those of 216 patients without central nervous system (CNS) involvement.ResultsResponse to T-DM1 treatment in BMs was available for 53 patients in the BM group (60.9%): two patients reported a complete response (3.8%), 11 patients obtained partial response (20.7%; overall response rate: 24.5%), 16 patients had a stable disease (30.1%). Regarding extracranial disease, a total of 77 and 191 patients were evaluable for response in BM group and non-BM group, respectively. The overall response rate was 35.1% in the BM group and 38.3% in the non-BM group; disease control rate was 53.3% and 66.6%, respectively.At a median follow-up of 16 months (range: 1–55), median cumulative progression-free survival (PFS) was 7 months (95% CI: 5.4–8.6) in the BM group and 8 months (95% CI: 5.7–10.3) in the non-BM group. In the second-line setting, PFS was 5 (95% CI: 3.1–6.9) versus 11 (95% CI: 7.1–14.9) months (p = 0.01). Overall survival was 14 months (95% CI: 12.2–15.8) in the BM group and 32 months (95% CI: 24.4–39.6) in the non-BM group (p < 0.0001).ConclusionsT-DM1 is active in breast cancer patients with BMs.     

Sequential versus concurrent anthracyclines and taxanes as adjuvant chemotherapy of early breast cancer: a meta-analysis of phase III randomized control trials

PurposeWe performed a meta-analysis of Phase III randomized trials to compare treatment outcomes for early-stage breast cancer patients receiving adjuvant chemotherapy with sequential or concurrent anthracyclines and taxanes.MethodsAll Phase III randomized trials comparing adjuvant chemotherapy of sequential or concurrent anthracyclines and taxanes in early-stage breast cancer patients were considered eligible. A total of three trials that enrolled 8728 women were analyzed. A pooled analysis was accomplished and event-based risk ratios (RR) with 95% confidence intervals (95%CI) were derived. The significant differences in disease-free survival (DFS) and overall survival (OS) were explored. A heterogeneity test was applied as well.ResultsAmong three eligible trials, significant differences in favor of sequential regimen were seen in DFS (RR: 0.90; 95%CI: 0.84 to 0.98; P = 0.01) and in OS (RR: 0.88; 95%CI: 0.79 to 0.98; P = 0.02).ConclusionConsidering all the available Phase III trials, sequential adjuvant chemotherapy for early breast cancer seems to add a significant benefit in both DFS and OS over concurrent regimens.     

The clinical impact of the American College of Surgeons Oncology Group Z-0011 trial – Results from the BreastSurgANZ National Breast Cancer Audit

IntroductionThe publication of the American College of Surgeons Oncology Group (ACOSOG) Z-0011 Trial concluded that axillary lymph node clearance is no longer necessary for women having breast conserving treatment with 1–2 positive axillary sentinel lymph glands. The current study was designed to investigate the clinical impact of the Z-0011 Trial in breast surgical practice.Materials and methodsThe BreastSurgANZ National Breast Cancer Audit database was interrogated for women treated between 2005 and 2010 who would have met the entry criteria for the Z-0011 Trial. This group was then calculated as a proportion of the total breast cancer episodes treated during this period.ResultsA total of 64,883 cases of breast cancer were eligible for analysis. 22,731 underwent breast conserving surgery and sentinel node biopsy for invasive breast cancer. A total of 4482 cases (6.9%) fulfilled the criteria for Z-11 Trial.ConclusionAlthough the ACOSOG Z-0011 Trial has important implications for sentinel node positive cases undergoing breast conserving treatment, the overall impact of the Trial in breast clinical practice is small. It cannot be described as “practice changing”. Women who fulfil the entry criteria for the Z-0011 Trial should be informed of the clinical relevance of the trial and be permitted to participate in informed discussions with members of the multidisciplinary team regarding their treatment options.     

Selective use of whole breast radiotherapy after breast conserving surgery for invasive breast cancer and DCIS

BackgroundRadiotherapy following breast conservation is routine in the treatment of invasive breast cancer and is commonly used in ductal carcinoma in situ to decrease local recurrence. However, adjuvant breast radiotherapy has significant short and longer-term side effects and consumes substantial health care resources. We aimed to review the randomised controlled trials and attempted to identify clinico-pathological factors and molecular markers associated with the risk of local recurrence.MethodsA literature search using the Medline and Ovid databases between 1965 and 2011 was conducted using the terms ‘breast conservation’ and radiotherapy, and radiotherapy and DCIS. Only papers with randomised clinical trials published in English in adult were included. Only Level 2 evidence and above was included.ResultsThree meta-analyses and 17 randomised controlled trials have been published in invasive disease and one meta-analysis and four randomised controlled trials for DCIS. Overall, adjuvant radiotherapy provides a 15.7% decrease in local recurrence and 3.8% decrease in 15-year risk of breast cancer death. The key clinico-pathological factors, which enable stratification into high, intermediate or low risk groups include age, oestrogen receptor positivity, use of tamoxifen and extent of surgery. Absolute reductions in 15-year risk of breast cancer death in these three prediction categories are 7.8%, 1·1%, and 0·1% respectively Adjuvant radiotherapy provides a 60% risk reduction in local recurrence in DCIS with no impact on distal metastases or overall survival. Size, pathological subtype and margins are major risk factors for local recurrence in DCIS.ConclusionsAdjuvant radiotherapy consistently decreases local recurrence across all subtypes of invasive and in-situ disease. While it has a survival advantage in those with invasive disease, this is not seen with DCIS and is minimal in invasive disease where the risk of local recurrence is low. This group includes women over 70 with node negative, ER positive tumours<2 cm.     

Prognosis of pregnancy after breast cancer diagnosis according to the type of treatment: A population-based study in Korea by the SMARTSHIP group

BackgroundsIn this study, we evaluated the incidence and outcomes of pregnancy after breast cancer was diagnosed in women of childbearing age. Additionally, we evaluated the prognosis of patients who became pregnant after breast cancer, according to the treatment.MethodsThis was a retrospective cohort study of women aged 20–45 years who were surgically treated for breast cancer between 2004 and 2014 using the Korean National Health Insurance database. The patients were classified into six groups according to the treatment. Propensity score matching was applied to the cohort to analyze the risk of breast cancer-associated mortality after pregnancy and childbirth.ResultsOf the 45,765 patients who had been newly diagnosed with breast cancer, 1826 (4%) became pregnant after breast cancer diagnosis. Among the pregnant group, the HR of the risk of death was 0.15 (95% CI, 0.06 to 0.36) for patients who became pregnant ≥49 months after the diagnosis. In patients who received endocrine therapy and chemotherapy, the pregnant group had better prognosis than the non-pregnant group. There was no significant difference between the pregnant group and the non-pregnant group in patients who received chemotherapy and trastuzumab with or without endocrine therapy.ConclusionThe risk of death was low in women who became pregnant ≥49 months after the diagnosis of breast cancer. The prognosis of pregnant women was non-inferior to that of non-pregnant women, even in women who received trastuzumab. These findings provide reassurance to patients with HER2-positive cancer who are considering future pregnancy.     

A prognostic factor index for overall survival in patients receiving first-line chemotherapy for HER2-negative advanced breast cancer: An analysis of the ATHENA trial

BackgroundEvidence-based definitions of ‘poor-prognosis’ or ‘aggressive’ advanced breast cancer are lacking.Patients and methodsWe developed a prognostic factor index using data from 2203 patients treated with first-line chemotherapy plus bevacizumab for HER2-negative advanced breast cancer.ResultsThe risk factors most closely associated with worse OS were: disease-free interval ≤24 months; liver metastases or ≥3 involved organ sites; prior anthracycline and/or taxane therapy; triple-negative breast cancer (TNBC); and performance status 2 or prior analgesic/corticosteroid treatment. Risk of death was increased threefold in patients with ≥3 versus ≤1 risk factors (hazard ratio 3.0 [95% CI 2.6–3.4; p < 0.001]; median 16.0 vs 38.8 months, respectively).ConclusionsThis prognostic index may enable identification of patients with a poorer prognosis in whom more intensive systemic regimens may be appropriate. The index may also be considered in designing new trials, although it requires validation in other datasets before extrapolation to non-bevacizumab-containing therapy.ClinicalTrials.gov identifier: NCT00448591.     

Central nervous system disease in phase III studies for advanced HER2 positive breast cancer: A review

ImportanceThe introduction of human epidermal growth factor receptor 2 (HER2) directed therapy has transformed the outcomes of patients with advanced breast cancer (BC). However, HER2 positive breast cancer has a predilection for the central nervous system (CNS) which is associated with significant morbidity and mortality. Understanding the intracranial activity of novel HER2 directed agents is key to developing treatments as well as possible preventative strategies for HER2-positive CNS disease.ObservationsUsing protocols and data from published phase III clinical trials for locally advanced/metastatic HER2-positive breast cancer since the licensing of single agent trastuzumab for advanced BC we review the central nervous system related aspects. This includes CNS related entry criteria, use of baseline and on study cross-sectional imaging of the CNS and protocol and non-protocol defined CNS end points and reported data.Conclusionsand Relevance: This review found heterogeneity between studies with regard to the entry criteria, use of CNS imaging and reported end points within the pivotal phase III studies. Based on these data, a standardisation of both entry criteria and end points with regard to the CNS should be developed and applied to future studies of HER2-positive advanced BC. Such an approach would enable the generation of comparable data and allow a meaningful analysis of different treatment approaches with regard to the CNS. This in turn would allow the development of the most optimal treatment approaches for HER2 positive CNS disease and ultimately the development of preventative strategies.     

Clinical characteristics of breast cancer patients with mental disorders

BackgroundSevere mental disorders are thought to affect the diagnosis and treatment of breast cancer because of their lower awareness and understanding of the disease and their reduced ability to cooperate with medical staff. We analyzed the clinical features of patients with breast cancer and pre-existing mental disorders such as schizophrenia, dementia, and intellectual disability. Patients and methods: We reviewed the records of 46 patients who were diagnosed with schizophrenia, dementia, or intellectual disability, before being diagnosed with breast cancer. Three patients had more than 2 mental disorders. All patients underwent curative surgical treatment between September 1992 and January 2015. Patients' clinicopathological information was compared with a control group of 727 breast-cancer patients without mental disorders seen during the same period.ResultsPatients with mental disorders were less likely to be aware of their own breast cancer; the lesions were often found by other people such as family, care staff, and medical staff. Breast cancer patients with mental disorders had significantly more advanced T factors and overall stage at the time of surgery than their counterparts without mental illness, more patients underwent total mastectomy, and fewer patients underwent postoperative adjuvant chemotherapy and radiation. Biological markers such as estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) expression were not significantly different between groups. Disease-free survival and overall survival were not significantly different between groups.ConclusionPatients with mental disorders receive less postoperative adjuvant chemotherapy; however, their outcomes were not worse than those of patients without mental disorders.     

Concurrent treatment with gonadotropin-releasing hormone agonists for chemotherapy-induced ovarian damage in premenopausal women with breast cancer: A meta-analysis of randomized controlled trials

BackgroundWhile chemotherapy significantly improves the prognosis of breast cancer patients, it also damages otherwise healthy organs, such as the ovaries. Gonadotropin-releasing hormone (GnRH) agonists may have a protective effect against chemotherapy-induced ovarian toxicity in premenopausal women being treated for breast cancer; however, studies of its clinical efficacy have reported conflicting results.ObjectivesThis meta-analysis was designed to assess the collective data from previous studies of GnRH agonists administered concurrently with chemotherapy to prevent chemotherapy-induced ovarian toxicity in premenopausal women with breast cancer.MethodsElectronic literature databases (Cochrane Library, Medline, and Embase) were searched for relevant randomized controlled trials (RCTs) published prior to April 2012. Only RCTs that compared GnRH agonists plus chemotherapy to chemotherapy alone for premenopausal women with breast cancer were selected. A random-effects model was used to calculate the risk ratios (RRs) for premature ovarian failure (POF) within one year after chemotherapy treatment and rates of resumed menses and spontaneous pregnancy during the follow-up period after cessation of treatment.ResultsFive RCTs composed of 528 patients (GnRH agonist combination, n = 274; chemotherapy alone, n = 254) were included in the meta-analysis. Significantly fewer women treated with GnRH agonist experienced post-chemotherapy POF, yielding a RR of 0.40 (vs. chemotherapy alone, 95% confidence interval [CI] 0.21–0.75). In contrast, both treatment groups experienced similar rates of resumed menses (RR = 1.31, 95% CI 0.93–1.85) and spontaneous pregnancy (RR = 0.96, 95% CI 0.20–4.56).ConclusionConcurrent administration of GnRH agonists during chemotherapy treatment of breast cancer in premenopausal women appears to protect against chemotherapy-related POF in the first year after treatment, but appears to have no effect on resumed menses or spontaneous pregnancy rates.     

Breast-conserving surgery using an inframammary fold incision technique for breast cancer

Background: Breast-conserving surgery is an established alternative for the majority of women with early stage breast cancer. Consensus on negative margins (no ink on tumour) for invasive cancer makes mutilating extensive lumpectomies unnecessary. Several breast-conserving surgical methods are described in the literature. The aim of this study was to describe and evaluate a technique using the inframammary fold incision.

Methods: Twenty-seven patients with suspected breast cancer (stage I–II) underwent breast-conserving surgery using the inframammary fold incision. Data regarding tumour characteristics, margin status, complications, oncologic and aesthetic outcome was analysed retrospectively.

Results: After a median follow-up of 35 months, 23 of the 24 patients with breast cancer (95.8%) had no evidence of disease. Post-operative complications (as defined by infection requiring antibiotic treatment and/or seroma requiring drainage) were seen in three of the 27 patients (11.1%). The final pathological examination revealed a positive excision margin in four patients (16.7%). Post-operative evaluation with the BREAST-Q? BCT module showed a mean RASCH score of 72.5 regarding ‘Satisfaction with breast’. The aesthetic result with a hidden scar is exemplified.

Conclusion: Breast-conserving surgery using the inframammary fold incision seems to be a safe method with better cosmesis; however, further research is needed.     

Impact of selective use of breast MRI on surgical decision-making in women with newly diagnosed operable breast cancer

BackgroundThis study evaluated the impact of breast MRI on surgical planning in selected cases of breast malignancy (invasive cancer or DCIS). MRI was used when there was ambiguity on clinical and/or conventional imaging assessment.MethodsConsecutive women with breast malignancy undergoing breast MRI were included. Clinical, mammogram and ultrasound findings and surgical plan before and after MRI were recorded. MRI findings and histopathology results were documented and the impact of MRI on treatment planning was evaluated.ResultsMRI was performed in 181/1416 (12.8%) cases (invasive cancer 155/1219 (12.7%), DCIS 26/197 (13.2%)). Indications for MRI were: clinically dense breast tissue difficult to assess (n = 66; 36.5%), discordant clinical/conventional imaging assessment (n = 61; 33.7%), invasive lobular carcinoma in clinically dense breast tissue (n = 22; 12.2%), palpable/mass-forming DCIS (n = 11; 6.1%); other (n = 19; 10.5%). The recall rate for assessment of additional lesions was 35% (63/181). Additional biopsy-proven malignancy was found in 11/29 (37.9%) ipsilateral breast recalls and 8/34 (23.5%) contralateral breast recalls. MRI detected contralateral malignancy (unsuspected on conventional imaging) in 5/179 (2.8%). The additional information from MRI changed management in 69/181 (38.1%), with more unilateral surgery (wider excision or mastectomy) in 53/181 (29.3%), change to bilateral surgery in 12/181 (6.6%), less surgery in 4/181 (2.2%). Clinical examination estimated histological size within 20 mm in 57%, conventional imaging in 55% and MRI in 71%.ConclusionMRI was most likely to show concordance with histopathology in the ‘discordant assessment’ and ‘invasive lobular’ groups and less likely for ‘challenging clinically dense breast tissue.’ MRI changed management in 69/181 (38.1%).     

Unresected screen-detected ductal carcinoma in situ: Outcomes of 311 women in the Forget-Me-Not 2 study

Background and aimThe natural history of ductal carcinoma in situ (DCIS) is poorly understood. The aim of this cohort study was to determine the outcomes of women who had no surgery for screen-detected DCIS in the 6 months following diagnosis.MethodsEnglish breast screening databases were retrospectively searched for women diagnosed with DCIS without invasive cancer at screening and who had no record of surgery within 6 months of diagnosis. These were cross-referenced with cancer registry data. Details of the potentially eligible women were sent to the relevant breast screening units for verification and for completion of data forms detailing clinical, radiological and pathological findings, non-surgical treatment and subsequent clinical course.ResultsData for 311 eligible women (median age 62 years) were available. 60 women developed invasive cancer, 56 ipsilateral and 4 contralateral. Ipsilateral invasion risk increased approximately linearly with time for at least 10 years. The 10-year cumulative risk of ipsilateral invasion was 9% (95% CI 4–21%), 39% (24–58%) and 36% (24–50%) for low, intermediate and high grade DCIS respectively and was higher in younger women, in those with larger DCIS lesions and in those with microinvasion. Most invasive cancers that developed were grade 2 or 3.ConclusionThe findings suggest that active surveillance may be a reasonable alternative to surgery in patients with low grade DCIS but that women with intermediate or high grade disease should continue to be offered surgery. This highlights the importance of reproducible grading of DCIS to ensure patients receive appropriate treatment.     

Challenges and Opportunities for Real-World Evidence in Metastatic Luminal Breast Cancer

BackgroundThe therapeutic armamentarium for patients with metastatic breast cancer is becoming more and more specific. Recommendations from clinical trials are not available for all treatment situations and patient subgroups, and it is therefore important to collect real-world data.SummaryTo develop recommendations for up-to-date treatments and participation in clinical trials for patients with metastatic breast cancer, the Prospective Academic Translational Research PRAEGNANT Network was established to optimize the quality of oncological care in the advanced therapeutic setting. The main aim of PRAEGNANT is to systematically record medical care for patients with metastatic breast cancer in the real-life setting, including the outcome and side effects of different treatment strategies, to monitor quality-of-life changes during therapy, to identify patients eligible for participation in clinical studies, and to allow targeted therapies based on the molecular structures of breast carcinomas.Key MessagesThis article describes the PRAEGNANT network and sheds light on the question of whether the various end points from clinical trials can be transferred to the real-world treatment situation.     

Outcomes of systemic therapy for advanced triple-negative breast cancer: A single centre experience

BackgroundPrognosis is worse for advanced triple-negative breast cancer (aTNBC) compared to other disease subtypes. Trials describe treatment outcomes in single specified lines of therapy; but few data describe treatment outcomes across the whole treatment pathway, which is critical in determining when patients should be referred for trials and to inform discussion. We evaluated treatment outcomes for aTNBC (overall response rate [ORR], median progression-free survival [mPFS] and median overall survival [mOS]) in patients treated largely outside of clinical trials.MethodsWe retrospectively identified 268 patients diagnosed with aTNBC from 01/12/2011 to 30/11/2016 from our electronic records and recorded patients' and tumour characteristics and treatment outcomes. Chi-squared/Fishers exact test and Kaplan-Meier statistical methods were utilised.Results186 patients treated with ≥1 line of systemic treatment were eligible and had median age of 55 (range 26–91). 53.8% had ECOG Performance Status 0 and 69.9% visceral involvement. 38.6% had disease-free interval (DFI)≤12 months following surgery or adjuvant chemotherapy completion and 14.0% had de-novo advanced disease. 11.4% carried a BRCA mutation. 64.5% received two lines of therapy, 37.6% three and 21.5% four.ORR and mPFS were 43.9% and 3.7 months for first-line therapy, 40.2% and 3.5 months for second-line, 28.8% and 2.5 months for third-line and 25.0% and 2.1 months for fourth-line. In first line, DFI>12 months was associated with higher ORR and longer PFS compared DFI ≤12 months.ConclusionsThe observed response rates are consistent with literature. However, PFS is short, and early consideration of clinical trials can be justified in these patients.