Canned Fish Consumption and Upper Digestive Tract Cancers.

Canned fish is a widely consumed and affordable food whose effect on cancer risk has been little investigated. We studied its effect on risk of upper digestive tract cancers using data from a network of hospital-based case-control studies from Northern Italy providing information about canned fish consumption as a separate item and including a total of 946 patients with oral cavity and pharynx cancer, 304 patients with esophageal cancer, 230 patients with gastric cancer and 3273 controls. Twenty-three percent of patients with cancer of the oral cavity or pharynx and 26% of those with cancer of the stomach consumed ≥1 serving per week of canned fish, compared to 40% and 49% of the respective control group. Among cases of esophageal cancer and controls 22% consumed ≥1 serving per week of canned fish. Odds ratios for ≥1 vs <1 portion per week were 0.79 (95% Confidence Interval, CI: 0.64-0.97) for cancer of the oral cavity and pharynx, and 0.59 (95% CI: 0.41-0.86) for stomach cancer, whereas there was no inverse association with esophageal cancer. These findings suggest a favorable role of canned fish for selected upper digestive tract cancers.

Bortezomib, cyclophosphamide, dexamethasone versus lenalidomide, cyclophosphamide, dexamethasone in multiple myeloma patients at first relapse.

Bortezomib- and lenalidomide-containing regimens are well-established therapies in multiple myeloma (MM). However, despite their extensive use, head-to-head comparisons have never been performed. Therefore, we compared bortezomib and lenalidomide in fixed-duration therapies. In this open-label, phase III study, we randomized MM patients at first relapse to receive either nine cycles of bortezomib plus cyclophosphamide plus dexamethasone (VCD) or lenalidomide plus cyclophosphamide plus dexamethasone (RCD). The primary endpoint was achievement of a very good partial response (VGPR) or better at six weeks after nine treatment cycles. From March 2011 to February 2015, 155 patients were randomized. VGPR or better was achieved by 12 patients (15%) in the VCD arm and 14 patients (18%) in the RCD arm (P = 0·70). Median progression-free survival (PFS) was 16·3 (95% CI: 12·1-22·4) with VCD and 18·6 months (95% CI: 14·7-25·5) with RCD, and the two-year overall survival (OS) was 75% (95% CI: 66-86%) and 74% (95% CI: 64-85%) respectively. In subgroup analyses, no differences in PFS were observed in bortezomib- and lenalidomide-naïve patients, nor in patients who received a bortezomib-based regimen in first line. Adverse events were consistent with the well-established safety profiles of both drugs. Bortezomib and lenalidomide treatments were equally effective in terms of depth of response, PFS, and OS in MM patients at first relapse.

Appropriateness of prescription of oral anticoagulant therapy in acutely hospitalized older people with atrial fibrillation. Secondary analysis of the SIM-AF cluster randomized clinical trial.

AIMS: To assess the appropriateness of oral anticoagulant (OAC) prescription and its associated factors in acutely hospitalized elderly patients. METHODS: Data were obtained from the prospective phase of SIM-AF (SIMulation-based technologies to improve the appropriate use of oral anticoagulants in hospitalized elderly patients with Atrial Fibrillation) randomized controlled trial, aimed to test whether an educational intervention improved OAC prescription, compared to current clinical practice, in internal medicine wards. In this secondary analysis, appropriateness of OAC prescription was assessed at hospital admission and discharge. RESULTS: For 246 patients, no significant differences were found between arms (odds ratio 1.38, 95% confidence interval [CI] 0.84-2.28) in terms of appropriateness of OAC prescription. Globally, 92 patients (37.4%, 95% CI = 31.6-43.6%) were inappropriately prescribed or not prescribed at hospital discharge. Among 51 patients inappropriately prescribed, 82% showed errors on dosage, being mainly under-dosed (n = 29, 56.9%), and among 41 inappropriately not prescribed, 98% were taking an antiplatelet drug. Factors independently associated with a lower probability of appropriateness at discharge were those related to a higher risk of bleeding (older age, higher levels of aspartate aminotransferase, history of falls, alcohol consumption) and antiplatelet prescription at admission. The prescription of OACs at admission was the strongest predictor of appropriateness at discharge (odds ratio = 7.43, 95% CI = 4.04-13.73). CONCLUSIONS: A high proportion of hospitalized older patients with AF remains inappropriately prescribed or nonprescribed with OACs. The management of these patients at hospital admission is the strongest predictor of prescription appropriateness at discharge.

Appropriateness of antiplatelet therapy for primary and secondary cardio- and cerebrovascular prevention in acutely hospitalized older people.

AIMS: Antiplatelet therapy is recommended for the secondary prevention of cardio- and cerebrovascular disease, but for primary prevention it is advised only in patients at very high risk. With this background, this study aims to assess the appropriateness of antiplatelet therapy in acutely hospitalized older people according to their risk profile. METHODS: Data were obtained from the REPOSI register held in Italian and Spanish internal medicine and geriatric wards in 2012 and 2014. Hospitalized patients aged ≥65 assessable at discharge were selected. Appropriateness of the antiplatelet therapy was evaluated according to their primary or secondary cardiovascular prevention profiles. RESULTS: Of 2535 enrolled patients, 2199 were assessable at discharge. Overall 959 (43.6%, 95% CI 41.5-45.7) were prescribed an antiplatelet drug, aspirin being the most frequently chosen. Among patients prescribed for primary prevention, just over half were inappropriately prescribed (52.1%), being mainly overprescribed (155/209 patients, 74.2%). On the other hand, there was also a high rate of inappropriate underprescription in the context of secondary prevention (222/726 patients, 30.6%, 95% CI 27.3-34.0%). CONCLUSIONS: This study carried out in acutely hospitalized older people shows a high degree of inappropriate prescription among patients prescribed with antiplatelets for primary prevention, mainly due to overprescription. Further, a large proportion of patients who had had overt cardio- or cerebrovascular disease were underprescribed, in spite of the established benefits of antiplatelet drugs in the context of secondary prevention.

The recurrence pattern following delayed breast reconstruction after mastectomy for breast cancer suggests a systemic effect of surgery on occult dormant micrometastases.

The purpose of this study was to characterize the recurrence dynamics in breast cancer patients after delayed reconstruction. We hypothesized that surgical reconstruction might stimulate dormant micrometastases and reduce time to recurrence. All mastectomy breast cancer patients with delayed surgical reconstruction at Haukeland University Hospital, between 1977 and 2007, n = 312, were studied. Our control group consisted of 1341 breast cancer patients without reconstruction. For each case, all patients in the control group with identical T and N stages and age ±2 years were considered. A paired control was randomly selected from this group. 10 years after primary surgery, 39 of the cases had relapsed, compared to 52 of the matched controls. The reconstructed group was analyzed for relapse dynamics after mastectomy; the first peak in relapses was similarly timed, but smaller than for the controls, while the second peak was similar in time and size. Second, the relapse pattern was analyzed with reconstruction as the starting point. A peak in recurrences was found after 18 months, and a lower peak at the 5th-6th year. The height of the peak correlated with the extent of surgery and initial T and N stages. Timing of the peak was not affected, neither was the cumulative effect. The relapse pattern, when time origin is placed both at mastectomy and at reconstruction, is bimodal with a peak position at the same time points, at 2 years and at 5-6 years. The timing of the transition from dormant micrometastases into clinically detectable macrometastases might be explained by an enhancing effect of surgery.

Statins, ACE/ARBs drug use, and risk of pneumonia in hospitalized older patients: a retrospective cohort study.

The aims of this study is to evaluate the association between angiotensin-converting enzyme inhibitor (ACE-I), angiotensin II receptor blocker (ARBs) and/or statin use with the risk of pneumonia, as well as and with in-hospital and short-term outpatient mortality in hospitalized older patients with pneumonia. Patients aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro Politerapuie SIMI-Società Italiana di Medicina Interna) register from 2010 to 2019 were screened to assess the diagnosis of pneumonia and classified on whether or not they were prescribed with at least one drug among ACE-I, ARBs, and/or statins. Further study outcomes were mortality during hospital stay and at 3 months after hospital discharge. Among 5717 cases included (of whom 18.0% with pneumonia), 2915 (51.0%) were prescribed at least one drug among ACE-I, ARBs, and statins. An inverse association was found between treatment with ACE-I or ARBs and pneumonia (OR = 0.79, 95% CI 0.65-0.95). A higher effect was found among patients treated with ACE-I or ARBs in combination with statins (OR = 0.67, 95% CI 0.52-0.85). This study confirmed in the real-world setting that these largely used medications may reduce the risk of pneumonia in older people, who chronically take them for cardiovascular conditions.

Nailfold capillaroscopy in systemic sclerosis: data from the EULAR scleroderma trials and research (EUSTAR) database.

OBJECTIVE: The aims of this study were to obtain cross-sectional data on capillaroscopy in an international multi-center cohort of Systemic Sclerosis (SSc) and to investigate the frequency of the capillaroscopic patterns and their disease-phenotype associations. METHODS: Data collected between June 2004 and October 2011 in the EULAR Scleroderma Trials and Research (EUSTAR) registry were examined. Patients' profiles based on clinical and laboratory data were obtained by cluster analysis and the association between profiles and capillaroscopy was investigated by multinomial logistic regression. RESULTS: 62 of the 110 EUSTAR centers entered data on capillaroscopy in the EUSTAR database. 376 of the 2754 patients (13.65%) were classified as scleroderma pattern absent, but non-specific capillary abnormalities were noted in 55.48% of the cases. Four major patients' profiles were identified characterized by a progressive severity for skin involvement, as well as an increased number of systemic manifestations. The "early" and "active" scleroderma patterns were generally observed in patients with mild/moderate skin involvement and a low number of disease manifestations, while the "late" scleroderma pattern was found more frequently in the more severe forms of the disease. CONCLUSION: These data indicate the importance of capillaroscopy in SSc management and that capillaroscopic patterns are directly related to the extent of organ involvement.

Significance of ipsilateral breast tumor recurrence after breast conserving treatment: role of surgical removal.

OBJECTIVE: To analyze the pattern over time (dynamics) of further recurrence and death after ipsilateral breast tumor recurrence (IBTR) in breast cancer patients undergoing breast conserving treatment (BCT). METHODS: A total of 338 evaluable patients experiencing IBTR were extracted from a database of 3,293 patients undergoing BCT. The hazard rates for recurrence and mortality throughout 10 years of follow-up after IBTR were assessed and were compared to the analogous estimates associated to the primary treatment. RESULTS: In a time frame with the time origin at the surgical treatment for IBTR, the hazard rate for further recurrence displays a bimodal pattern (peaks at the second and at the sixth year). Patients receiving mastectomy for IBTR reveal recurrence and mortality dynamics similar to that of node positive (N+) patients receiving mastectomy as primary surgery, apart from the first two-three years, when IBTR patients do worse. If the patients with time to IBTR longer than 2.5 years are considered, differences disappear. CONCLUSIONS: The recurrence and mortality dynamics following IBTR surgical removal is similar to the corresponding dynamics following primary tumor removal. In particular, patients with time to IBTR in excess of 2.5 years behave like N+ patients following primary tumor removal. Findings may be suitably explained by assuming that the surgical manoeuvre required by IBTR treatment is able to activate a sudden growing phase for tumor foci most of which, as suggested by the systemic model of breast cancer, would have reached the clinical level according to their own dynamics.

Appropriateness of the Prescription and Use of Medicines: An Old Concept but More Relevant than Ever.

The availability of drugs to treat diseases, control symptoms, or prevent their onset is one of the most important resources for maintaining health [...].

Antidiabetic Drug Prescription Pattern in Hospitalized Older Patients with Diabetes.

OBJECTIVE: To describe the prescription pattern of antidiabetic and cardiovascular drugs in a cohort of hospitalized older patients with diabetes. METHODS: Patients with diabetes aged 65 years or older hospitalized in internal medicine and/or geriatric wards throughout Italy and enrolled in the REPOSI (REgistro POliterapuie SIMI-Società Italiana di Medicina Interna) registry from 2010 to 2019 and discharged alive were included. RESULTS: Among 1703 patients with diabetes, 1433 (84.2%) were on treatment with at least one antidiabetic drug at hospital admission, mainly prescribed as monotherapy with insulin (28.3%) or metformin (19.2%). The proportion of treated patients decreased at discharge (N = 1309, 76.9%), with a significant reduction over time. Among those prescribed, the proportion of those with insulin alone increased over time (p = 0.0066), while the proportion of those prescribed sulfonylureas decreased (p < 0.0001). Among patients receiving antidiabetic therapy at discharge, 1063 (81.2%) were also prescribed cardiovascular drugs, mainly with an antihypertensive drug alone or in combination (N = 777, 73.1%). CONCLUSION: The management of older patients with diabetes in a hospital setting is often sub-optimal, as shown by the increasing trend in insulin at discharge, even if an overall improvement has been highlighted by the prevalent decrease in sulfonylureas prescription.

Prescription appropriateness of anticoagulant drugs for prophylaxis of venous thromboembolism in hospitalized multimorbid older patients.

The aims were to assess: the prescription prevalence of anticoagulant drugs for thromboprophylaxis (TP) in hospitalized older patients; the appropriateness of their prescription or non-prescription; the in-hospital mortality in appropriately versus non-appropriately prescribed or not prescribed patients. 4836 patients aged 65 or older, admitted to the Italian internal medicine and geriatric wards participating to the REPOSI register from 2012 to 2019 were assessed for prescription of anticoagulant drugs for TP at admission and/or during hospital stay. The Padua Prediction Score (PPS) and the IMPROVE score were used to assess the thrombotic and bleeding risk. Patients were considered to be appropriately prescribed when had PPS ≥ 4 and IMPROVE < 7, and appropriately not prescribed when PPS < 4. Logistic regression model was used to assess whether appropriateness was associated with in-hospital mortality. Among 4836 patients included, anticoagulants were prescribed for TP in 1233 (25.5%). In all, 4461 patients were assessable for appropriateness: 3136 (70.3%) were appropriately prescribed or non-prescribed according to their thrombotic and bleeding risk. Among 1138 patients receiving prophylaxis, only 360 (31.7%) were appropriately prescribed, while among 3323 non-prescribed patients, 2776 (83.5%) were appropriately non-prescribed. The in-hospital mortality rate was lower in patients appropriately prescribed or non-prescribed than in those inappropriately prescribed or non-prescribed (OR: 0.63; 95% CI: 0.46-0.83). In conclusion, a high prevalence of multimorbid hospitalized patients were appropriately prescribed or non-prescribed for TP with anticoagulants, appropriate non-prescription being mainly driven by a high bleeding risk. The appropriateness of prescription or non-prescription was associated with lower in-hospital mortality.

Epidemiology of Serratia marcescens infections in NICU of a Teaching and Research Hospital in Northern Italy.

BACKGROUND: Serratia marcescens (Sm) is a known cause of infection and colonization in neonates receiving intensive care. The aim of this study was to identify the risk factors for colonization and infection with Sm in Neonatal Intensive Care Unit (NICU) of a tertiary care Hospital. METHODS: A case-control study was conducted from January to December 2011 in neonates admitted to the NICU. Cases are patients with a microbiologically confirmed infection or colonization, controls were randomly chosen among patients admitted to the same NICU. RESULTS: Globally, 39 acquired infections or colonizations were identified. Among factors related to pregnancy, only premature delivery was independently associated to the risk of infection; as well as mechanical ventilation and catheterization for parenteral nutrition, considering indwelling devices. Prolonged administration with antibiotics were also related to the risk of infection. Among Sm strains which have been tested to antibiotics, all have been resistant to amoxicillin/clavulanic acid and to colistin. CONCLUSIONS: This study confirms the association between Sm infection or colonization and low gestational age. Invasive medical devices and medications, strictly necessary in care-support of preterm neonates, are likely related to Sm infection too. Preventive control strategies are expected to be effective in the control of Sm spread in NICUs.

Axillary dissection versus no axillary dissection in older patients with T1N0 breast cancer: 15-year results of a randomized controlled trial.

OBJECTIVE: To assess the role of axillary dissection in older breast cancer patients with a clinically clear axilla. BACKGROUND: Axillary dissection, once standard treatment for breast cancer, is associated with considerable morbidity. It has been substituted by sentinel node biopsy with dissection only if the sentinel node is positive. We aimed to determine whether axillary surgery can be omitted in older women, thereby sparing them morbidity, without compromising long-term disease control. METHODS: We carried out a randomized clinical trial on 238 older (65-80 years) breast cancer patients, with clinically N0 disease of radiographic diameter 2 cm or less. Patients were randomized to quadrantectomy with or without axillary dissection. All received radiotherapy to the residual breast but not the axilla; all were prescribed tamoxifen for 5 years. Main outcome measures were overall survival and breast cancer mortality. We also assessed overt axillary disease in those who did not receive axillary dissection. RESULTS: After 15 years of follow-up, distant metastasis rate, overall survival, and breast cancer mortality in the axillary dissection and no axillary dissection arms were indistinguishable. The 15-year cumulative incidence of overt axillary disease in the no axillary dissection arm was only 6%. CONCLUSIONS: Older patients with early breast cancer and a clinically clear axilla treated by conservative surgery, postoperative radiotherapy, and adjuvant tamoxifen do not benefit from axillary dissection. This study was registered at clinicaltrials.gov (ID NCT00002720).

Multiple Medication Adherence and Related Outcomes in Community-Dwelling Older People on Chronic Polypharmacy: A Retrospective Cohort Study on Administrative Claims Data.

Poor medication adherence compromises treatment efficacy and adversely affects patients' clinical outcomes. This study aims to assess (1) multiple medication adherence to the most common drug classes chronically prescribed to older people, (2) the factors associated, and (3) the clinical outcomes. This retrospective cohort study included 122,655 community-dwelling patients aged 65-94 years old, newly exposed to chronic polypharmacy, and recorded in the Lombardy Region (northern Italy) administrative database from 2016 to 2018. Multiple medication adherence was assessed for drugs for diabetes, antithrombotics, antihypertensives, statins, and bisphosphonates, by calculating the daily polypharmacy possession ratio (DPPR). One-year mortality, nursing home, emergency department (ED), and hospital admission rates were calculated for 2019. The most prescribed drugs were antihypertensives (89.0%). The mean (std.dev) DPPR was 82.9% (15.6). Being female (OR = 0.85, 95%CI: 0.84-0.86), age ≥85 years (OR = 0.77, 95%CI: 0.76-0.79), and multimorbidity (≥4 diseases, OR = 0.88, 95%CI: 0.86-0.90) were associated with lower medication adherence. A higher DPPR was associated with clinical outcomes-in particular, improved survival (HR = 0.93 for 10/100-point increase, 95%CI: 0.92-0.94) and lower incidence in nursing home admissions (SDHR = 0.95, 95%CI: 0.93-0.97). Adherence to the most common chronic drugs co-prescribed to the older population was high. Better multiple medication adherence was associated with better clinical outcomes.

Prescription Appropriateness of Drugs for Peptic Ulcer and Gastro-Esophageal Reflux Disease: Baseline Assessment in the LAPTOP-PPI Cluster Randomized Trial.

Background: Drugs for peptic ulcer and gastro-esophageal reflux disease (GERD) are among the most widely prescribed, frequently without appropriate indications. This represents an important issue, as it leads to risk of adverse events for patients and unnecessary costs for National Health Service. Aim: To assess the prescription appropriateness of drugs for GERD, in the frame of the "Evaluation of the effectiveness of a Low-cost informative intervention to improve the Appropriate PrescripTiOn of Proton PumP Inhibitors in older people in primary care: a cluster-randomized controlled study" (LAPTOP-PPI) (Clinicaltrial.gov: NCT04637750). Methods: The appropriateness of drug prescription was assessed on data collected in administrative databases, by integrating information on concomitant medications, outpatient medical and laboratory procedures and hospital discharge diagnoses, according to the reimbursement criteria provided by the Italian Medicine Agency. We analyzed data of community-dwelling people aged 65 years and over, living in the areas of Bergamo (Northern Italy) and Caserta (Southern Italy), from July 1 to 31 December 2019. Results: Among 380,218 patients, 175,342 (46.1%) received at least one prescription of drugs for GERD. All in all, we found that only 41.2% of patients received appropriate prescriptions. Conclusion: Given the potential risk of adverse drug reactions, especially in older people, educational interventions should be prompted for physicians, in order to improve the quality of prescription of drugs for GERD and, in turn, avoid unfavorable health outcomes and unnecessary costs.

Inverse Association between Canned Fish Consumption and Colorectal Cancer Risk: Analysis of Two Large Case-Control Studies.

Fish is among the foods exerting favourable effects on colorectal cancer (CRC), but the possible role of canned fish has been insufficiently investigated. We aimed to investigate the relationship between canned fish consumption and CRC risk. We analysed data from two case−control studies conducted between 1992 and 2010 in several Italian areas, comprising a total of 2419 incident cases and 4723 hospital controls. Canned fish consumption was analysed according to the weekly frequency of consumption as <1 serving per week (s/w) (reference category), 1 < 2 s/w, and ≥2 s/w. We calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression models, adjusting for several recognised confounding factors. Overall, canned fish consumption was lower among cases than among controls (23.8% vs. 28.6%). An inverse association was found between canned fish consumption and CRC risk with a significant trend in risk (OR = 0.81, 95% CI: 0.71−0.92 for intermediate consumption and OR = 0.66, 95% CI: 0.51−0.85 for the highest one), which was consistent across strata of several covariates. This study is the first to offer a basis of support for canned fish consumption as a component of a healthy diet, and it has relevant public health implications given the high ranking of CRC in incidence and mortality worldwide.

Medication adherence in community-dwelling older people exposed to chronic polypharmacy.

BACKGROUND: To evaluate medication adherence and associated factors of seven of the most common drug classes prescribed to community-dwelling older people. METHODS: This is a retrospective cohort study on medication adherence in community-dwelling older people (65-94 years old) on chronic polypharmacy and recorded from 2013 to 2015 in the administrative database of the Lombardy region (Northern Italy). Adherence was assessed for diabetic drugs, antithrombotic agents, drugs acting on the renin-angiotensin system, statins, bisphosphonates, antidepressants and drugs for obstructive airway diseases by calculating the medication possession ratio (MPR). Patients were then divided in fully (MPR ≥80%), partially (40%≤MPR<80%) and poorly adherent (10%

Use of Lipid-Lowering Drugs and Associated Outcomes According to Health State Profiles in Hospitalized Older Patients.

OBJECTIVE: To assess how lipid-lowering drugs (LLDs) are administered in the hospitalized patients aged 65 and older and their association with clinical outcomes according to their health-related profiles. DESIGN: This is a retrospective study based on data from REPOSI (REgistro POliterapie SIMI - Italian Society of Internal Medicine) register, an Italian network of internal medicine hospital wards. SETTING AND PARTICIPANTS: A total of 4642 patients with a mean age of 79 years enrolled between 2010 and 2018. METHODS: Socio-demographic characteristics, functional abilities, cognitive skills, laboratory parameters and comorbidities were used to investigate the health state profiles by using multiple correspondence analysis and clustering. Logistic regression was used to assess whether LLD prescription was associated with patients' health state profiles and with short-term mortality. RESULTS: Four clusters of patients were identified according to their health state: two of them (Cluster III and IV) were the epitome of frailty conditions with poor short-term outcomes, whereas the others included healthier patients. The average prevalence of LLD use was 27.6%. The lowest prevalence was found among the healthier patients in Cluster I and among the oldest frail patients with severe functional and cognitive impairment in Cluster IV. The highest prevalence was among multimorbid patients in Cluster III (OR=4.50, 95% CI=3.76-5.38) characterized by a high cardiovascular risk. Being prescribed with LLDs was associated with a lower 3-month mortality, even after adjusting for cluster assignment (OR=0.59; 95% CI = 0.44-0.80). CONCLUSION: The prevalence of LLD prescription was low and in overall agreement with guideline recommendations and with respect to patients' health state profiles.

Recurrence and mortality dynamics for breast cancer patients undergoing mastectomy according to estrogen receptor status: different mortality but similar recurrence.

(Cancer Sci 2010; 101: 826-830) The purpose was to ascertain whether the recurrence risk patterns for patients with estrogen receptor (ER)-positive (P) and ER-negative (N) breast cancer support the ER-related clinical divergence suggested by the observed different mortality patterns and gene expression profiles. Both recurrence and death were considered in a series of 771 patients undergoing mastectomy. ER status was available for 539 patients. The hazard rates for recurrence and mortality throughout 15 years of follow-up were assessed. The recurrence dynamics displays a bimodal pattern for both ERP and ERN tumors with comparable peak timings. The two curves cross during the 3rd year. By contrast, the mortality dynamics are definitely different for ERP and ERN tumors: during the early follow-up period ERN patients have their highest mortality risk, while ERP patients have their lowest mortality risk. The two curves cross during the 5th year. In spite of the different mortality dynamics, the recurrence dynamics do not demonstrate a major distinction in timing between ERP and ERN breast cancers, suggesting that the metastasis development process following mastectomy is apparently similar for both ER categories. The observed differences in the mortality risk are plausibly attributable to ER-related factors influencing the clinical course from recurrence to death. These clinical findings apparently contradict the occurrence of two different types of breast cancer, notwithstanding the distinct epidemiological, clinical, and molecular features linked to ERP and ERN tumors, although ER levels may concur to establish the event risk levels.

Recurrence and mortality according to estrogen receptor status for breast cancer patients undergoing conservative surgery. Ipsilateral breast tumour recurrence dynamics provides clues for tumour biology within the residual breast.

BACKGROUND: The study was designed to determine how tumour hormone receptor status affects the subsequent pattern over time (dynamics) of breast cancer recurrence and death following conservative primary breast cancer resection. METHODS: Time span from primary resection until both first recurrence and death were considered among 2825 patients undergoing conservative surgery with or without breast radiotherapy. The hazard rates for ipsilateral breast tumour recurrence (IBTR), distant metastasis (DM) and mortality throughout 10 years of follow-up were assessed. RESULTS: DM dynamics displays the same bimodal pattern (first early peak at about 24 months, second late peak at the sixth-seventh year) for both estrogen receptor (ER) positive (P) and negative (N) tumours and for all local treatments and metastatic sites. The hazard rates for IBTR maintain the bimodal pattern for ERP and ERN tumours; however, each IBTR recurrence peak for ERP tumours is delayed in comparison to the corresponding timing of recurrence peaks for ERN tumours. Mortality dynamics is markedly different for ERP and ERN tumours with more early deaths among patients with ERN than among patients with ERP primary tumours. CONCLUSION: DM dynamics is not influenced by the extent of conservative primary tumour resection and is similar for both ER phenotypes across different metastatic sites, suggesting similar mechanisms for tumour development at distant sites despite apparently different microenvironments. The IBTR risk peak delay observed in ERP tumours is an exception to the common recurrence risk rhythm. This suggests that the microenvironment within the residual breast tissue may enforce more stringent constraints upon ERP breast tumour cell growth than other tissues, prolonging the latency of IBTR. This local environment is, however, apparently less constraining to ERN cells, as IBTR dynamics is similar to the corresponding recurrence dynamics among other distant tissues.