Adverse impact of regional lymph node involvement in osteosarcoma

BackgroundMetastatic dissemination in osteosarcoma occurs haematogenously, though regional lymph node involvement is rarely reported. We investigated incidence, patient characteristics and survival for patients with osteosarcoma and regional lymph node involvement at diagnosis.MethodsWe identified 2748 cases of high-grade osteosarcoma with available information regarding regional lymph node involvement in the Surveillance Epidemiology and End Results database from 1973 to 2009. Demographics were compared using chi-squared tests or t-tests. Overall survival was estimated using Kaplan–Meier method and compared with log-rank tests. Multivariate analysis of overall survival was performed using Cox proportional hazards methods.ResultsThere were 74 patients (2.7%) with regional lymph node involvement at diagnosis of whom 19 (0.7%) were pathologically confirmed. Patients with regional node involvement were more likely to have extraskeletal tumours, distant metastases, tumours arising outside the lower extremity (p < 0.0001 for all comparisons) and larger tumours (p = 0.033). Five-year overall survival in those with and without regional node involvement was 10.9% (95% confidence interval (CI) 4.6–20.4) and 54.3% (95% CI 52.2–56.4; p < 0.0001). In multivariate analysis, regional node involvement remained predictive of inferior survival after controlling for differences in metastatic status, age, tumour site and extraskeletal origin (hazard ratio 2.05, 95% CI 1.57–2.67; p < 0.0001). Similar survival results were found when the analysis was restricted to patients with pathologically confirmed positive or negative regional lymph nodes.ConclusionThis analysis confirms that regional node involvement is a significant adverse prognostic factor that is independent of metastatic status, extraskeletal origin, age and tumour site.     

Quantitative analysis of changes in ER,PR and HER2 expression in primary breast cancer and paired nodal metastases

BackgroundAssessment of receptors [estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2)] is routinely carried out on primary tumour in order to select appropriate adjuvant therapy; the same analysis is not carried out on nodal metastases. Since de novo resistance to therapy is common, we quantified differences in receptor expression between primary and nodal disease in order to assess whether this might contribute to therapeutic resistance.Patients and methodsA total of 385 patients with invasive primary breast carcinomas and paired lymph nodes (n = 211) were assessed for ER, PR and HER2 expression using quantitative immunofluorescence. Cut-points were defined by comparison with tumours scored by immunohistochemistry (IHC) and FISH. Differences in expression for each of the markers and molecular phenotype were analysed.ResultsQuantitative receptor expression shows a wide dynamic range compared with IHC. Overall, 46.9% cases had disparate breast/node receptor status of at least one receptor. Many of the differences in expression between primary tumour and node are large magnitude (greater than fivefold) changes. Triple-negative phenotype changes in 23.1% of cases.ConclusionsA significant number of patients show discordant quantitative expression of molecular markers between primary and nodal disease. Appropriately measured, lymph node receptor status could be a more accurate measurement for guiding adjuvant therapy, which requires testing in a clinical trial.     

Is primary tumour resection associated with survival improvement in patients with colorectal cancer and unresectable synchronous metastases? A pooled analysis of individual data from four randomised trials

ObjectiveTo evaluate the impact on survival of primary tumour resection in patients with unresectable synchronous metastases from colorectal cancer (CRC).Summary background dataPrimary tumour resection in this setting remains controversial.Patients and methodsWe retrieved individual data of 1155 patients with metastatic CRC included in four first-line chemotherapy trials: Fédération Francophone de Cancérologie Digestive (FFCD)-9601, FFCD-2000-05, Actions Concertées dans les cancers COloRectaux et Digestifs (ACCORD)-13, and ML-16987. Patients with unresectable synchronous metastases were eligible for this study. We used univariate and multivariate analyses (Cox models stratified on the trial) to assess the impact of primary tumour resection and other potential prognostic variables on overall survival (OS) (the primary endpoint).ResultsAmongst the 1155 patients, 810 patients met the inclusion criteria and 59% (n = 478) underwent resection of their primary tumour, prior to trial entry (resection group). Compared to patients in the non-resection group (n = 332 [41%]), those in the resection group were more likely to have a colonic primary, lower baseline carcinoembryonic antigen (CEA) and alkaline phosphatase levels, and normal white-blood-cell count (p < 0.001 each). Primary tumour resection was independently associated to better OS in multivariate analysis (hazard ratio (HR), 0.63 [0.53–0.75]; p < 0.001, with a more favourable impact of resection on OS in case of rectal primary and low CEA level. Primary tumour resection was also independently associated to a better progression-free survival in multivariate analysis (HR, 0.82 [0.70–0.95]; p < 0.001).ConclusionPrimary tumour resection was independently associated to a better OS in patients with CRC and unresectable synchronous metastases.     

Impact of primary tumour resection on survival of patients with colorectal cancer and synchronous metastases treated by chemotherapy: Results from the multicenter,randomised trial Fédération Francophone de Cancérologie Digestive 9601

ObjectiveTo assess the impact of primary tumour resection on overall survival (OS) of patients diagnosed with stage IV colorectal cancer (CRC).DesignAmong the 294 patients with non-resectable colorectal metastases enrolled in the Fédération Francophone de Cancérologie Digestive (FFCD) 9601 phase III trial, which compared different first-line single-agent chemotherapy regimens, 216 patients (73%) presented with synchronous metastases at study entry and constituted the present study population. Potential baseline prognostic variables including prior primary tumour resection were assessed by univariate and multivariate Cox analyses. Progression-free survival (PFS) and OS curves were compared with the logrank test.ResultsAmong the 216 patients with stage IV CRC (median follow-up, 33 months), 156 patients (72%) had undergone resection of their primary tumour prior to study entry. The resection and non-resection groups did not differ for baseline characteristics except for primary tumour location (rectum, 14% versus 35%; p = 0.0006). In multivariate analysis, resection of the primary was the strongest independent prognostic factor for PFS (hazard ratio (HR), 0.5; 95% confidence interval [CI], 0.4–0.8; p = 0.0002) and OS (HR, 0.4; CI, 0.3–0.6; p < 0.0001). Both median PFS (5.1 [4.6–5.6] versus 2.9 [2.2–4.1] months; p = 0.001) and OS (16.3 [13.7–19.2] versus 9.6 [7.4–12.5]; p < 0.0001) were significantly higher in the resection group. These differences in patient survival were maintained after exclusion of patients with rectal primary (n = 43).ConclusionResection of the primary tumour may be associated with longer PFS and OS in patients with stage IV CRC starting first-line, single-agent chemotherapy.     

Obesity increases the incidence of distant metastases in oestrogen receptor-negative human epidermal growth factor receptor 2-positive breast cancer patients

BackgroundObesity is a major negative determinant of breast cancer outcome. However, there are contrasting data on the differential impact of obesity on specific breast cancer subtypes. In particular, very little is known on human epidermal growth factor receptor 2-positive (HER2+) tumours.Patients and methodsWe assessed the prognostic role of increased body mass index (BMI) on a consecutive series of non-metastatic HER2+ patients treated at our institution before the introduction of adjuvant Trastuzumab. We separately analysed oestrogen receptor-positive (ER+) and -negative (ER?) HER2+ cases.ResultsIn ER?/HER2+ tumours we observed a significantly worse overall survival (Hazard ratio (HR) 1.79, p-value 0.041) and cumulative incidence of distant metastases (HR 2.03, p-value 0.019) in obese (BMI > 30) versus normal/underweight (BMI < 25) patients. Local relapses appeared to be non-significantly reduced in obese patients, masking the overall effect on disease-free survival. Outcome in ER+ tumours, instead, was not significantly different between BMI groups.ConclusionsObesity significantly correlates with worse overall survival and cumulative incidence of distant metastases in ER?/HER2 positive breast cancer. Differences in the biology of breast tumours may determine individual susceptibility to obesity. The biology of the underlying tumour should be taken into account in the design of dietary intervention trials in breast cancer.     

Elevated expression of HMGB1 in squamous-cell carcinoma of the head and neck and its clinical significance

PurposeHMGB1 overexpression has been reported in a variety of human cancers. However, the role of HMGB1 in squamous-cell carcinoma of the head and neck (SCCHN) remains unclear. The aim of the present investigation was to analyse HMGB1 protein expression in both SCCHN tissue and cell levels and to assess its prognostic significance in SCCHN.MethodsHMGB1 protein expression in 103 primary SCCHN tissue specimens was analysed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, HMGB1 protein expression was evaluated in cell level by Western blotting.ResultsBy Western blotting analysis, all the 5 SCCHN cell lines overexpressed HMGB1 protein, whereas the non-transformed immortalised cell line NP-69 had relatively weak HMGB1 protein expression. Immunohistochemical staining revealed that HMGB1 protein was detected in 91 (91/103, 88.3%) primary tumour samples, but only in 7 (7/16, 43.75%) adjacent non-carcinoma samples (p < 0.001); moreover, HMGB1 overexpression was significantly associated with T classification (p = 0.001), clinical stage (p < 0.001), recurrence (p < 0.001) and lymph node metastasis (p < 0.001). Survival analysis demonstrated that high HMGB1 expression was significantly associated with shorter disease-free and overall survival (both p < 0.001), especially in late patients with SCCHN. When HMGB1 expression and lymph node status were combined, patients with HMGB1 overexpression/lymph node (+) had both poorer disease-free and overall survival than others (both p < 0.001). Multivariate analysis further demonstrated that HMGB1 was an independent prognostic factor for patients with SCCHN.ConclusionsHMGB1 protein may contribute to the malignant progression of SCCHN, and present as a novel prognostic marker and a potential therapeutic target for patients with SCCHN.     

Tumour CD133 mRNA expression and clinical outcome in surgically resected colorectal cancer patients

BackgroundHuman prominin-1 (CD133) is a novel pentaspan membrane protein which was originally classified as a marker of primitive haematopoietic and neural stem cells. Cancer stem cells have been isolated and expanded from leukaemia and several solid tumours, and have been associated with metastasis, chemoresistance and relapse. CD133 is recognised as a stem cell marker and is capable of identifying a tumour-initiating subpopulation in brain, colon, melanoma and other solid tumours.MethodsWe assessed CD133 mRNA expression levels by RT-QPCR in tumour and matched normal tissue from 64 stages I–III colorectal cancer (CRC) patients and correlated tumour CD133 levels with clinicopathological characteristics and clinical outcome.ResultsIn four patients, CD133 mRNA was not expressed in tumour or in normal tissue. In the remaining 60 patients, expression levels were higher in tumour than in normal tissue (p = 0.001). Higher levels of CD133 expression were associated with shorter relapse-free interval (RFI) (p = 0.004) and overall survival (OS) (p < 0.0001). In the multivariate analyses, CD133 levels emerged as a prognostic marker for RFI and OS.ConclusionsWe have observed longer RFI and OS in patients with lower levels of CD133, regardless of adjuvant treatment and other clinical characteristics. If these findings are confirmed in larger prospective studies, CD133 assessment may prove useful for new diagnostic and therapeutic procedures for CRC patients.     

A meta-analysis of oestrogen receptor,progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases

BackgroundThe discordance in oestrogen receptor (ER), progesterone receptor (PgR) and human epidermal growth factor receptor 2 (HER2) status between primary and recurrent breast cancer is being intensively investigated and a large amount of data have been produced. However, results from different studies are heterogeneous and often conflicting. To highlight this issue, a meta-analysis of published data was performed.MethodsA literature search was performed using Medline, and all the studies published from 1983 to 2011 comparing changes in ER, PgR and/or HER2 status in patients with matched breast primary and recurrent tumours were included. We used random-effects models to estimate pooled discordance proportions.ResultsWe selected 48 articles, mostly reporting retrospective studies. Thirty-three, 24 and 31 articles were focused on ER, PgR and HER2 changes, respectively. A total of 4200, 2739 and 2987 tumours were evaluated for ER, PgR and HER2 discordance, respectively. The heterogeneity between study-specific discordance proportions was high for ER (I² = 91%, p < 0.0001), PgR (I² = 79%, p < 0.0001) and HER2 (I² = 77%, p < 0.0001). Pooled discordance proportions were 20% (95% confidence interval (CI): 16–35%) for ER, 33% (95% CI: 29–38%) for PgR and 8% (95% CI: 6–10%) for HER2. Pooled proportions of tumours shifting from positive to negative and from negative to positive were 24% and 14% for ER (p = 0.0183), respectively. The same figures were 46% and 15% for PgR (p < 0.0001), and 13% and 5% for HER2 (p = 0.0004).ConclusionOur findings strengthen the concept that changes in receptor expression may occur during the natural history of breast cancer, suggesting clinical implications and a possible impact on treatment choice.     

Intramammary lymph node metastasis predicts poorer survival in breast cancer patients

Involvement of an intramammary lymph node with metastatic breast cancer is an uncommon clinical or radiological presentation. Previously reported series of patients are small in number and the clinical advice is unclear.We identified 100 patients on our pathology database with intramammary lymph nodes in association with a primary breast cancer. Ten were identified pre-operatively on breast imaging and 90 were first discovered on pathological assessment of excised breast tissue. Twenty one contained metastasis. Factors that predicted for intramammary node metastasis were increasing age (p = 0.017), lymphovascular invasion (p = 0.002) and grade of tumour (p = 0.012). The presence of metastasis within the intramammary lymph node was associated with a poorer disease free survival (p = 0.007) and reduced overall survival (p = 0.035). Sixty seven percent of patients with intramammary node metastasis had further axillary metastases. One patient had an intramammary node metastasis but uninvolved axillary sentinel node. She presented 19 months later with an axillary nodal recurrence.The presence of intramammary lymph node metastasis is associated with poorer outcome in breast cancer patients. Pre-operative detection of intramammary lymph node metastasis is helpful to guide breast and axillary surgeries. Intramammary lymph node metastasis predicts strongly for axillary metastatic disease and axillary node clearance is recommended.     

Prognostic significance of ploidy and S-phase fraction in primary intraoral squamous cell carcinoma and their corresponding metastatic lymph nodes

BackgroundDespite improvements in diagnosis and therapy of oral and oro-pharyngeal carcinomas during the past 30 years the 5-year disease-free survival is still poor. Patient’s prognosis is affected by cervical lymph node metastasis rather than primary tumors. The DNA ploidy and S-phase fraction (SPF) are associated with tumor aggressiveness and patient outcome in many solid tumors.PurposeAnalysis of DNA ploidy and SPF in primary oral squamous cell carcinoma (OSCC) and corresponding node metastasis as prognostic markers in relation to conventional prognostic factors and disease-free survival (DFS).MethodsPloidy status and SPF (mean value) of 37 formalin-fixed paraffin embedded (FFPE) primary OSCC tumors and their corresponding lymph node metastasis were assessed by flow cytometry (FCM) and correlated with clinicopathologic prognostic parameters and DFS.ResultsMost of OSCC tumors (86.5%) were Grade II. Among primary OSCC the incidence of aneuploidy was 19%, 51.4% showed high SPF (>10.62%) and 48.6% had low SPF (<10.62%). Border line significance (P = 0.10) was detected between ploidy status and SPF in primary tumors. In lymph node metastases all tumors were diploid, 78.4% of metastatic tumors revealed low SPF and only 21.6% showed high SPF. There was a statistically significant correlation (p = 0.02) between site of tumors and DFS and a highly statistically significant correlation (p = 0.01) between SPF of primary tumors and DFS.ConclusionsHigh SPF of primary OSCC tumors assessed by FCM was significantly associated with decreased disease free survival rates. DNA ploidy showed no relationship to bad prognostic indicators in either primary OSCC or their metastatic tumors.     

Tumoural expression and circulating level of VEGFR-3 (Flt-4) in metastatic melanoma patients: Correlation with clinical parameters and outcome

PurposeThe presence of metastases in regional lymph nodes is a strong indicator of poor patient survival in many types of cancer. It has recently been shown that vascular endothelial growth factor-C (VEGF-C), and its receptor VEGFR-3, may play a pivotal role in the promotion of metastasis to regional lymph nodes. This study was designed to detect and evaluate whether the expression of VEGFR-3 or its soluble form plays a role in metastatic malignant melanoma and to determine the relationship with clinicopathological parameters and patients outcome.Experimental designVEGFR-3 expression on melanoma tumour was evaluated by immunohistochemical study. Using a sensitive enzyme-linked immunosorbent assay, sVEGFR-3 was measured in sera of 60 metastatic melanoma patients in comparison with 30 healthy controls.ResultsImmunohistochemical study demonstrated a high expression of VEGFR-3 in melanoma cells. Median level of pre-treatment sVEGFR-3 was significantly higher (p = 0.00001) in melanoma patients as compared to healthy donors. No association was noted between VEGFR-3 in situ or in sera and gender, age or LDH level. Median serum VEGFR-3 levels were significantly higher in patients with high tumour burden as compared to those with low tumour burden (p = 0.013) as well as in non-responding patients (n = 33) as compared to responding ones (n = 27). Finally, low level of VEGFR-3 was also related positively to disease free survival (X² = 3.85, p = 0.022).ConclusionThese results suggest that the expression and high pre-treatment sVEGFR-3 level are significantly correlated to poorer prognosis, and may be promising targets for new therapeutic strategies in melanoma disease.     

Prognostic relevance of disseminated tumour cells from the bone marrow of early stage breast cancer patients – Results from a large single-centre analysis

BackgroundThis is the largest single-centre study to determine the prognostic relevance of disseminated tumour cells (DTCs) from the bone marrow (BM) of stage I-III breast cancer patients. Additionally, we aimed to analyse the impact of DTC detection on adjuvant bisphosphonate (BP) treatment efficacy.MethodsBM aspirates were collected during primary surgery for early breast cancer (EBC; T1–4, N0–2, M0) at Tuebingen University, Germany, between January 2001 and January 2013. DTCs were identified by immunocytochemistry (pancytokeratin antibody A45/B-B3) and cytomorphology. We retrospectively estimated the influence of DTC detection and BP treatment on disease-free survival (DFS) and overall survival (OS) using univariate (log-rank test) and multivariate (cox regression) analysis.FindingsBM aspirates were available from 3141 patients. In 803 (26%) of these, DTCs were detectable. As compared to DTC-negative patients, DTC-positive patients more frequently had larger tumors (p < 0.001), lymph node involvement (p < 0.001), hormonal receptor positive tumours (p < 0.001) and HER2-positive tumours (p = 0.048). DTC-positive patients were at an increased risk of relapse (hazard ratio (HR) 1.74, 95% confidence interval (CI) 1.34–2.25, p < 0.001) and death (HR 1.44 95% CI 1.13–1.86, p = 0.004). In the multivariate analysis DTCs were an independent predictor of DSF and OS. Additionally, BP treatment had no significant influence on DFS or OS in DTC-negative patients, while it was significantly associated with increased DFS (p < 0.001) and OS (p = 0.006) in DTC-positive patients.InterpretationThese data confirm the clinical validity of DTCs from the BM for prognostication of early breast cancer patients. Further studies are warranted to determine whether DTCs are predictive for adjuvant treatment efficacy using bisphosphonates.     

Coexpression of biological key modulators in primary colorectal carcinomas and related metastatic sites: implications for treatment with cetuximab

BackgroundRecent studies suggested substantial differences between primary tumors and metastases for EGFR expression in colorectal cancer (CRC). The aim of the study was to correlate the expression of a panel of molecular markers between primary CRC samples and metastases.MethodsExpressions of EGFR, pEGFR, VEGF, pVEGF, PTEN, pAKT and p21 were analyzed in 28 primary tumors and 32 liver metastases by immunohistochemistry performed on formalin-fixed, paraffin-embedded sections from 46 CRC patients. The molecular profiles were evaluated by tissue micro-array. The correlation between tumor and metastasis biomarker expressions was tested.ResultsAmong 60 CRC samples, 25% were EGFR positive, 38% were pEGFR positive, 38%were VEGF positive, 48% were pVEGF positive, 70% were pAKT positive and 51%were p21 positive. PTEN was deleted in 39% of cases and absence of p21 expression was found in 49% of cases. Asignificant correlation was observed between primary tumors and metastases for pAKT (p = 0.037) and pEGFR (p = 0.0002) status. In patients treated with cetuximab-based therapy (n = 18), p21 appeared as a significant predictive factor of response (p = 0.036).ConclusionBiomarkers status may change between primary and metastatic sites in CRC, with potential implications for the identification of patients who are likely to respond to anti-EGFR treatment.     

Internal mammary sentinel nodes: Ignore,irradiate or operate?

IntroductionThis study describes the results of internal mammary chain (IMC) biopsy, identifying factors that predict ‘hot spots’ and nodal metastases for patients in whom mapped IMC nodes were routinely dissected.MethodsThe nodal basin and status of every axillary and IMC site identified by lymphoscintigraphy were examined. Binary logistic regression analysed the relationship of several patients and tumour factors with IMC hot spots and metastases.ResultsNinety of 490 patients (18.4%) had IMC sentinel lymph nodes (SLNs) identified by lymphatic mapping and dissected, and 20 of these (22.2%) were found to have metastases. Mapping to the IMC was most likely for women aged under 35 years (29.4%) (p = 0.117), women aged 35–44 (22.6%) (p = 0.034) or those with medial (23.7%) or central tumour location (22.2%) (p = 0.014; p = 0.062, respectively). Predictors of IMC positivity included age <35 years (p = 0.063), grade 3 histology (p = 0.018) and lymphatic vascular invasion (LVI) (p = 0.032). Although IMC positivity was more likely with positive axillary nodes, this trend was not significant.ConclusionWe identified several factors (age <35 years, tumour grade and LVI) that independently predict IMC SLN identification and positivity for patients with stage I or II breast cancer. Where IMC hot spots are not dissected, we predict IMC positivity of 50% or more for young women (<35 years) or women with high grade or LVI positive tumours, and these women may benefit from more intensive chemotherapy and radiotherapy to the IMC.     

Male breast cancer: A retrospective analysis

BackgroundTo evaluate our results in the treatment of male breast cancer patients with respect to local control (LC), overall survival (OS) and possible prognosis factors for survival.Patients and methodsThirty-nine patients with male breast cancer have been retrospectively studied with the trial aim to evaluate the results of our practice. Among them, 94.8% had invasive ductal carcinoma (IDC), 2.6% invasive papillary carcinoma (IPC) and 2.6% invasive lobular carcinoma (ILC) and the distribution according to stage was found to be 12.8, 46.2, 30.7 and 10.3% in Stages I, II, III and IV, respectively. Among the patients, 7.7% received radiotherapy (RT) and hormonotherapy (HT), 22.8% received chemotherapy (CT), 61.8% received chemoradiotherapy (CRT) and HT and 7.7% received HT in addition to surgery.ResultsThe distant metastases rate was 36% and the local recurrence rate was 5%. All the local recurrences and the distant metastases had occurred after the first two years. The five-year disease free survival (DFS) and OS rates were 65.8 and 80.1% respectively. In our series, univariate analysis for OS demonstrated statistical significance for lymph node metastases (p = 0.00001), stage (p = 0.0098) and age (p = 0.03); while RT in the treatment modality (p = 0.6849), and tumor size (p = 0.4439) demonstrated no significance. The presence of lymph node metastases significantly impairs OS (p = 0.004) and DFS (p = 0.014) in multivariate analysis.ConclusionPostoperative radiotherapy was important in the management of male breast cancer to improve LC resulting in one local failure, but did not improve OS and DFS in our analysis. The presence of lymph node metastases significantly impaired OS and DFS.     

Clonal alteration of breast cancer receptors between primary ductal carcinoma in situ (DCIS) and corresponding local events

BackgroundEmerging data propose biomarker alteration due to clonal selection between the primary invasive breast cancer and corresponding metastases. In addition, impact on survival has been demonstrated. The present study investigates the relationship between the oestrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) between primary ductal carcinoma in situ (DCIS) and intra-individually matched ipsilateral event.Materials and methodsThe cohort includes 1504 patients, diagnosed with a primary DCIS between 1986 and 2004. Of the 274 patients who developed a local relapse, 135 developed a new in situ carcinoma and 139 an invasive cancer up to 31st December 2011. ER and PR were identified by immunohistochemistry (IHC) and HER2 by silver-enhanced in situ hybridisation (SISH) as well as IHC.ResultsER (n = 112), PR (n = 113) and HER2 (n = 114) status from both the primary DCIS and the corresponding relapse were assessed and were demonstrated to be discordant in 15.1%, 29.2% and 10.5% respectively. The receptor conversion was both from negative to positive and from positive to negative with no general pattern being seen in spite of sub-dividing into in situ relapse and invasive relapse. However, primary DCIS was HER2 positive in 40.3% whereas in situ and invasive relapses were HER2 positive in 42.9% and 34.5% respectively.ConclusionsReceptor conversion for ER, PR and HER2 status occurred between primary DCIS and corresponding local relapse in 10–30%. This study could not confirm that HER2 overexpression in primary DCIS had any impact on tumour progression to invasive cancer which has been proposed.     

Breast cancer during follow-up and progression – A population based cohort on new cancers and changed biology

BackgroundEmerging data indicate an important role for biopsies of clinically/radiologically defined breast cancer ‘recurrences’. The present study investigates tumour related events (relapses, other malignancies, benign conditions) after a primary breast cancer diagnosis.Patients and methodsThe cohort includes 2102 women, representing all patients, with primary invasive breast cancer during 2000–2011 in the county of Värmland, Sweden. A comparative analysis of oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and proliferation (Ki67) between the primary tumour and the relapse was performed and related to outcome.ResultsWith a mean follow-up time of 4.8 years, 1060 out of 2102 patients have had a biopsy taken after the initial breast cancer diagnosis demonstrating 177 recurrences, 93 other malignancies (colorectal, lung, skin), 40 cancer in situ (skin, breast) and 857 benign lesions. Approximately 70% (177 out of 245) of all cases of relapsed breast cancer underwent a biopsy during this time period. For patients with recurrences, ER (n = 127), PR (n = 101), HER2 (n = 73) and Ki67 (n = 55) status in both primary tumour and the corresponding relapse were determined. The discordance of receptor status was 14.2%, 39.6%, 9.6% and 36.3%, respectively. Loss of ER or PR in the relapse resulted in a significant increased risk of death (hazard ratio (HR) 3.62; 95% confidence interval (CI), 1.65–7.94) and (HR 2.34; 95% CI, 1.01–5.47) compared with patients with stable ER or PR positive tumours. The proportion of patients losing ER was bigger in the group treated with endocrine therapy alone or in combination with chemotherapy, 16.7% and 13.3%, respectively, compared with the group treated with chemotherapy alone or that which received no treatment 4.3% and 7.7%, respectively.ConclusionDiscordance of biomarkers between the primary tumour and the corresponding relapse was seen in 10–40% of the patients, adjuvant therapies seem to drive clonal selections. Patients with tumours losing ER or PR during progression have worse survival compared with patients with retained receptor expression.