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Introduction Right heart thrombus (RiHTh) can be considered a rare and severe condition associated with thromboembolic phenomena. A case is described of a COVID-19 patient presenting with an isolated thrombus in the right ventricle. Case presentation An 80-years-old Caucasian male was admitted in an intensive care unit (ICU) for COVID-19 related acute respiratory distress syndrome. The patient showed signs of hemodynamic instability, elevated cardiac troponin I and altered coagulation. On further assessment, a thrombotic mass near the apex of the right ventricle was detected. Moreover, the apex and the anteroseptal wall of the right ventricle appeared akinetic. Following the administration of a therapeutic dose of unfractionated heparin over a forty-eight hour period, re-evaluation of the right chambers showed that the thrombotic mass had resolved entirely. Conclusion COVID-19 patients could constitute a population at risk of RiHTh. Routine use of echocardiography and a multidisciplinary approach can improve the management of this condition.

To determine whether a red clover preparation plus dietary intervention administered to premenopausal women with breast cancer (BC), improves menopausal symptoms due to anti-oestrogen treatment, and hence promotes compliance with tamoxifen, prevents weight gain and is safe. Surgically-treated premenopausal women with oestrogen receptor (ER) positive disease taking tamoxifen were recruited to a prospective double-blind randomized trial (NCT03844685). The red clover group (N = 42) received one oral tablet/day (Promensil® Forte) containing 80 mg red clover extract for 24 months. The placebo group (N = 39) received one oral tablet/day without active ingredient. All women were encouraged to follow a Mediterranean-type diet and keep active. Outcomes were Menopausal Rating Score (MRS), body mass index (BMI), waist and hip girth, insulin resistance, and levels of cholesterol, triglycerides, and sex hormones. As safety indicators, endometrial thickness, breast density, and effects of patient serum on ER-positive BC cell lines were investigated. MRS reduced significantly (p

Objective To ascertain, in cN0/1 breast cancer patients given primary chemotherapy followed by sentinel node biopsy (SNB), whether SNB alone is adequate axillary treatment if the sentinel nodes (SNs) are clear (pN0). Summary background data 2020 guidelines do not recommend SNB in most cN1 patients with clear SNs after primary chemotherapy because the high SNB false negative rate might lead to poorer outcomes. Methods We prospectively assigned SNB after primary chemotherapy to 353 consecutive cT2 cN0/1 patients, median age 47 years (range 22-76) treated from 2007 to 2015. If the SNs were pN0, patients generally received no further axillary treatment (SNB only); if the SNs were pN1, completion AD (SNB + AD) was usually performed. Primary outcomes were overall (OS) and disease-free (DFS) survival in SNB only vs SNB + AD patients, assessed by Kaplan-Meier and compared using log-rank test, with use of propensity scores to account for bias due to non-random assignment to SNB vs SNB + AD. Results Median follow-up was 108 months, interquartile range 66-136. OS and DFS did not differ significantly between the groups by propensity score-weighted comparison: 10-year OS 89% (95%CI: 81-99%) in SNB only patients vs 86% (95%CI: 78-95%) in SNB + AD patients; 10-year DFS 79% (95%CI: 68-92%) vs 69% (95%CI: 58-81%). No SNB-only patient developed axillary failure. Conclusions cT2 cN0/1 patients whose SNs are disease-free (pN0) after primary chemotherapy can be offered SNB (with no further axillary treatment if the SNs are negative), irrespective of axillary status beforehand, without affecting OS or DFS.

Electron positron collisions are a very promising environment to search for new physics, and in particular for dark sector related observables. The most challenging experimental problem in detecting dark sector candidates is the very high associated Standard Model background. For this reason it is important to identify observables that are, at the same time, minimally suppressed in the dark sector and highly suppressed in the Standard Model. One example is the $e^+ e^-\to 3(e^+e^-)$ process that can be mediated either by the production and subsequent decay of dark Higgs ($h'$), $e^+e^-\to A'h'\to 6e$ or produced by the Standards Model process $e^+ e^-\to 3(e^+e^-)$. In the following letter we study the relative contribution to observed $e^+ e^-\to 3(e^+e^-)$ total cross section, coming from the $h'$ mediated and from the Standard Model processes in the contest of fixed target and low energy collider experiments, with particular attention to the PADME experiment at the INFN Laboratori Nazionali di Frascati., Comment: 18 pages

Background It is controversial whether sentinel node biopsy (SNB) is adequate in breast cancer patients who become cN0 after primary chemotherapy. To address this we retrospectively compared outcomes in T2 cases given primary chemotherapy, comparing those given axillary dissection (AD) with those given SNB but no AD if sentinel nodes were clinically negative post-chemotherapy. Methods We examined overall survival (OS), disease-free survival (DFS), and axillary failure in 317 consecutive cT2 cN0/1 patients given primary chemotherapy followed by quadrantectomy/mastectomy, between January 2002 and December 2007. The approach to the axilla changed over time allowing division into three groups: 101 (31.9%) given upfront AD; 139 (43.8%) given SNB + AD; and 77 (24.3%) given SNB only because the SNs were negative. Results After median follow-ups of 92 (AD), 99 (SNB + AD) and 72 months (SNB-only), OS (p = 0.131) and DFS (p = 0.087) did not differ between the 3 groups, or between SNB-only and the ypN1 and ypN0 subgroups of SNB + AD, or between the cN0 and cN1 subgroups (before chemotherapy) of the SNB-only group. No SNB-only patient had axillary failure. OS (p = 0.004) and DFS (p = 0.002) were better in patients with complete response than those with partial response or stable/progressive disease. Conclusions SNB is adequate in T2 patients who are cN0 after primary chemotherapy, irrespective of axillary status before. Better outcomes after complete pathological remission confirm the prognostic importance of response to primary chemotherapy, and suggest that all T2 patients should receive primary chemotherapy.

Leptin has shown positive effects on respiratory function in experimental settings. The role of leptin on perioperative respiratory function in morbidly obese patients has not been established. We performed a retrospective analysis of morbidly obese patients undergoing laparoscopic sleeve gastrectomy. Fasting serum leptin and interleukin (IL)-6 were measured preoperatively, and arterial blood gases were obtained pre- and postoperatively. Outcome variables were arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and differences in PaO2 and PaCO2 between pre- and postoperative values (ΔPaO2, ΔPaCO2; postoperative minus preoperative). Patients with lower (

Purpose We evaluated whether 18F-3′-deoxy-3′-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT).

Background Sentinel node (SN) biopsy is the standard method to evaluate axillary node involvement in breast cancer (BC). Positron emission tomography with 2-(fluorine-18)-fluoro-2-deoxy-D-glucose (FDG-PET) provides a non-invasive tool to evaluate regional nodes in BC in a metabolic-dependent, biomolecular-related way. In 1999, we initiated a prospective non-randomized study to compare these two methods and to test the hypothesis that FDG-PET results reflect biomolecular characteristics of the primary tumor, thereby yielding valuable prognostic information. Patients and methods A total of 145 cT1N0 BC patients, aged 24–70 years, underwent FDG-PET and lymphoscintigraphy before surgery. SN biopsy was followed in all cases by complete axillary dissection. Pathologic evaluation in tissue sections for involvement of the SN and other non-SN nodes served as the basis of the comparison between FDG-PET imaging and SN biopsy. Results FDG-PET and SN biopsy sensitivity was 72.6% and 88.7%, respectively, and negative predictive values were 80.5% and 92.2%, respectively. A subgroup of more aggressive tumors (ER-GIII, Her2+) was found mainly in the FDG-PET true-positive (FDG-PET+) patients, whereas LuminalA, Mib1 low-rate BCs were significantly undetected ( p = 0.009) in FDG-PET false-negative (FDG-PET−) patients. Kaplan–Meier survival estimates after a median follow-up of more than 8 years showed significantly worse overall survival for FDG-PET+ patients in node-positive (N+) patients ( p = 0.035) as compared to N+/FDG-PET− patients, which overlapped with survival curves of N− and FDG-PET+ or − patients. Conclusions Our findings suggest that FDG-PET results reflect intrinsic biologic features of primary BC tumors and have prognostic value with respect to nodal metastases. FDG-PET false negative cases appear to identify less aggressive indolent metastases. The possibility to identify a subgroup of N+ BC patients with an outcome comparable with N− BC patients could reduce the surgical and adjuvant therapeutic intervention.

Background Our randomized trial found no survival advantage for axillary dissection (AD) compared observation only (no AD) in older patients with early breast cancer and a clinically negative axilla, indicating that AD is unnecessary. We compared characteristics and outcomes in out-trial patients with those in trial patients to provide indications as to whether AD can be safely omitted outside the trial setting. Methods The trial started in 1996, recruiting 238 patients age 65–80 years with cT1cN0 breast cancer, randomized to conservative surgery with or without AD. Over the recruitment period, 109 eligible patients who refused to participate in the trial, also received conservative breast surgery with or without AD depending on patient preference/surgeon opinion. Trial and out-trial patients received conventionally-fractioned whole breast radiation and tamoxifen for five years. Endpoints were breast cancer mortality, overall survival, and cumulative incidence of axillary disease in patients not receiving AD. Results After 15 years of follow-up, breast cancer mortality and overall survival did not differ between the AD and no AD arms, in either the trial or out-trial cohorts. The 15-year cumulative incidence of axillary relapse was 6% in the no AD arm of the trial group, and zero in the no AD arm of the out-trial group. Conclusions Outside the trial setting, older patients with T1N0 breast cancer can be safely treated by conservative surgery, postoperative radiotherapy and tamoxifen for five years (if ER-positive). Axillary surgery is appropriate only for the small proportion of patients who develop overt axillary disease during follow-up.

BACKGROUND Although axillary surgery is still considered to be a fundamental part of the management of early breast cancer, it may no longer be necessary either as treatment or as a guide to adjuvant treatment. The authors conducted a single-center randomized trial (INT09/98) to determine the impact of avoiding axillary surgery in patients with T1N0 breast cancer and planning chemotherapy based on biological factors of the primary tumor on long-term disease control. METHODS From June 1998 to June 2003, 565 patients aged 30 years to 65 years with T1N0 breast cancer were randomized to either quadrantectomy with (QUAD) or without (QU) axillary lymph node dissection; a total of 517 patients finally were evaluated. All patients received radiotherapy to the residual breast only. Chemotherapy for patients in the QUAD treatment arm was determined based on lymph node status, estrogen receptor status, and tumor grade. Chemotherapy for patients in the QU treatment arm was based on estrogen receptor status, tumor grade, and human epidermal growth factor receptor 2 and laminin receptor status. Overall survival (OS) was the primary endpoint. Disease-free survival (DFS) and rate and time of axillary lymph node recurrence in the QU treatment arm were the secondary endpoints. RESULTS After a median follow-up of >10 years, the estimated adjusted hazards ratio of the QUAD versus QU treatment arms for OS was 1.09 (95% confidence interval, 0.59-2.00; P = .783) and was 1.04 (95% confidence interval, 0.56-1.94; P = .898) for DFS. Of the 245 patients in the QU treatment arm, 22 (9.0%) experienced axillary lymph node recurrence. The median time to axillary lymph node recurrence from breast surgery was 30.0 months (interquartile range, 24.2 months-73.4 months). CONCLUSIONS Patients with T1N0 breast cancer did not appear to benefit in terms of DFS and OS from immediate axillary lymph node dissection in the current randomized trial. The biological characteristics of the primary tumor appear adequate for guiding adjuvant treatment. Cancer 2014;120:885–893. © 2013 American Cancer Society.

The present study investigated whether tumor markers such as cell proliferation and steroid receptor status, which have been shown to have relevance for important endpoints (relapse-free and overall survival), can also predict axillary disease in elderly patients with breast cancer. We evaluated 351 consecutive elderly women with breast cancer ≥70 years of age with estrogen receptor (ER)-positive tumors with no palpable axillary nodes, for whom information on cell proliferation determined by the 3H-thymidine labeling index (TLI) and progesterone receptor (PgR) was available. Patients underwent quadrantectomy (70.1%) or quadrantectomy plus radiotherapy (29.9%) without axillary node dissection, followed by adjuvant tamoxifen for at least 2 years. Univariable (cumulative incidence curves) and multivariable analyses (Fine and Gray models) were carried out. After a median follow-up of 16 years, ipsilateral axillary relapse was not related to PgR status but was strongly associated with tumor cell proliferation in both small (pT1) and large (pT2-4b) tumors. Axillary relapse cumulative incidence increased from 1% in patients with low-TLI (≤3%), PgR-positive and pT1 tumors to a maximum of 20% in patients with high-TLI, PgR-negative and pT2-4b tumors. Tumor cell proliferation, determined by TLI at primary surgery, is an important predictor of axillary relapse in elderly ER-positive breast cancer patients and could help to identify patients who should undergo axillary surgery.

To assess the role of axillary dissection in older breast cancer patients with a clinically clear axilla.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.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.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%.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).

To assess the long-term safety of no axillary clearance in elderly patients with breast cancer and nonpalpable axillary nodes.Lymph node evaluation in elderly patients with early breast cancer and clinically negative axillary nodes is controversial. Our randomized trial with 5-year follow-up showed no breast cancer mortality advantage for axillary clearance compared with observation in older patients with T1N0 disease.We further investigated axillary treatment in a retrospective analysis of 671 consecutive patients, aged ≥ 70 years, with operable breast cancer and a clinically clear axilla, treated between 1987 and 1992; 172 received and 499 did not receive axillary dissection; 20 mg/day tamoxifen was prescribed for at least 2 years. We used multivariable analysis to take account of the lack of randomization.After median follow-up of 15 years (interquartile range 14-17 years) there was no significant difference in breast cancer mortality between the axillary and no axillary clearance groups. Crude cumulative 15-year incidence of axillary disease in the no axillary dissection group was low: 5.8% overall and 3.7% for pT1 patients.Elderly patients with early breast cancer and clinically negative nodes did not benefit in terms of breast cancer mortality from immediate axillary dissection in this nonrandomized study. Sentinel node biopsy could also be foregone due to the very low cumulative incidence of axillary disease in this age group. Axillary dissection should be restricted to the small number of patients who later develop overt axillary disease.

Introduction TiLOOP® Bra is a permanent titanium-coated polypropylene mesh currently used in post-mastectomy breast reconstruction with implants. This mesh is generally presented as inducing low-grade inflammatory reactions, but only few reports focused on its possible side effects. In the case described here, the use of the mesh led to minor clinical problems that needed to be clinically and surgically managed at the same time as a local relapse. Case description A patient with high-grade ductal carcinoma in situ underwent primary surgery (nipple-sparing mastectomy and one-stage reconstruction using the TiLOOP® Bra mesh) and was subsequently referred for radiological and clinical investigation when various nodules became apparent during a follow-up physical examination. Prior to the histopathological proof, the diagnosis of local recurrence was complicated by the occurrence of an extensive granulomatous reaction in the fixation areas along with mild inflammatory changes scattered on the surface of the mesh. Discussion and evaluation This case illustrates a side effect of titanium-coated permanent mesh in immediate implant-based reconstruction, i.e. the formation of granulomas in the inframammary fold, probably in the area where the mesh had been folded or fixed. We propose a safer technical approach to avoid the problem and a clinical management strategy for patients at high risk of local recurrence who develop granuloma-like nodules. Conclusions A surgical technique is suggested to prevent granuloma formation. If, however, subcutaneous nodules that may be local recurrences do appear, they should not be interpreted by default as a granulomatous reaction, but should be fully investigated and possibly excised.

Background Whether radiotherapy (RT) is beneficial in elderly (⩾70years) patients undergoing conservative surgery for early breast cancer has long been controversial. Recent randomised trials show that most elderly patients do not benefit from RT. We started a prospective non-randomised trial to address this issue in 1987 and now present results for the 627 consecutive pT1/2cN0 patients recruited, and treated by conservative surgery (quadrantectomy) and tamoxifen, and assigned non-randomly to RT or no RT. Methods We used multivariate competing risks models to estimate 15-crude cumulative incidence (CCI) of ipsilateral breast tumour recurrence (IBTR), distant metastasis and breast cancer mortality. The models incorporated a propensity score as a measure of probability of receiving RT based on baseline characteristics, to account for the lack of randomisation. Results For pT1 patients, 15-year CCIs of IBTR, distant metastasis and breast cancer death were indistinguishable in the RT and no RT groups. For pT2 patients, 15-year CCI of IBTR was much higher in those not given RT (14.6% versus 0.8%, p =0.004), although breast cancer mortality and distant metastasis did not differ significantly between RT and no RT. Conclusions Consistent with the findings of recent randomised trials, our long-term data indicate that most elderly, ER-positive patients with pT1 cN0 breast cancer treated by quadrantectomy do not benefit from RT. The 14.6% CCI of IBTR in our pT2 patients is an additional finding not presented in the trials and suggests that RT should be administered to elderly patients with pT2 disease.

The problem of the search for a proportion of cured patients of breast cancer and the relative time to cure breast cancer has been known since the 1950s. The literature on this topic has developed during the last decades thanks to the availability of studies with long follow-up times, which was required by the type of disease in question. The aim of this study is to estimate, if it exists, the proportion of cured breast cancer patients with a parametric method accounting for competing causes of death.In this work we used data from a two-group randomized controlled trial. From 1973 to 1980, 701 women were recruited with breast cancer measuring no more than 2 cm in diameter. They were randomly assigned to radical mastectomy (349 patients) or breast-conserving surgery followed by radiotherapy to the ipsilateral mammary tissue (352 patients). Thanks to a reliable classification of the causes of death, it was possible to analyze data using cause-specific mortality.The parametric crude cumulative incidence estimates by the Gompertz distribution accorded closely with the non-parametric estimates. The analysis was also performed for subsets of patients based on menopausal status and number of positive lymph nodes. Statistical evidence for the existence of a cure fraction ranging from 0.48 to 0.71, depending on the subset, was found. However, the estimated proportion of cured patients has not been reached after 30 years' follow-up for most of the subsets.Although statistical evidence has been found for the presence of a cure fraction, in practical terms it seems that 30 years after a breast cancer diagnosis cure cannot yet be claimed.

We evaluated whether (18)F-3'-deoxy-3'-fluorothymidine positron emission tomography (FLT PET) can predict the final postoperative histopathological response in primary breast cancer after the first cycle of neoadjuvant chemotherapy (NCT).In this prospective cohort study of 15 patients with locally advanced operable breast cancer, FLT PET evaluations were performed before NCT, after the first cycle of NCT, and at the end of NCT. All patients subsequently underwent surgery. Variables from FLT PET examinations were correlated with postoperative histopathological results.At baseline, median of maximum standardized uptake values (SUVmax) in the groups showing a complete pathological response (pCR) + residual cancer burden (RCB) I, RCB II or RCB III did not differ significantly for the primary tumour (5.0 vs. 2.9 vs. 8.9, p = 0.293) or for axillary nodes (7.9 vs. 1.6 vs. 7.0, p = 0.363), whereas the Spearman correlation between SUVmax and Ki67 proliferation rate index was significant (r = 0.69, p 0.001). Analysis of the relative percentage change of SUVmaxin the primary tumour (∆SUVTmax(t₁)) and axillary nodes (∆SUVNmax(t₁)) after the first NCT cycle showed that the power of ∆SUVTmax(t 1) to predict pCR + RCB I responses (AUC = 0.91, p 0.001) was statistically significant, whereas ∆SUVNmax(t₁) had a moderate ability (AUC = 0.77, p = 0.119) to separate subjects with ΔSUVTmax(t₁) -52.9 % into two groups: RCB III patients and a heterogeneous group that included RCB I and RCB II patients. A predictive score μ based on ΔSUVTmax(t₁) and ΔSUVNmax(t₁) parameters is proposed.The preliminary findings of the present study suggest the potential utility of FLT PET scans for early monitoring of response to NCT and to formulate a therapeutic strategy consistent with the estimated efficacy of NCT. However, these results in a small patient population need to be validated in a larger independent cohort.

Breast cancer is a disease that affects women >70 years of age much more frequently than other age groups. Epidemiologic data show that more than 40% of breast cancers occur in the elderly. The optimal primary treatment for elderly patients with breast cancer is controversial and ranges from tamoxifen as sole therapy to surgery. Despite the high prevalence of the disease, the elderly have been excluded from clinical trials mainly for the presence of concurrent medical conditions that adversely affect treatment strategies. Since life expectancy continues to increase in western countries, an appropriate treatment that respects quality of life needs to be determined for the elderly age group. In the light of randomised and retrospective studies carried out to date, limited surgery without axillary dissection plus adjuvant tamoxifen seems to achieve, mainly for elderly patients with early stage breast cancer, a local-regional control rate comparable to that obtained with more aggressive therapeutic strategies. The results of ongoing prospective clinical trials will show whether or not conservative surgery without axillary clearance and tamoxifen may be routinely used for elderly patients with early breast cancer.

A fundamental question in surgery of only magnetic resonance imaging (MRI)-detected breast lesions is to ensure their removal when they are not palpable by clinical examination and surgical exploration. This is especially relevant in the case of small tumors, carcinoma in situ or lobular carcinoma. Thirty-nine patients were enrolled in the study, 21 patients with breast lesions detected by both conventional imaging and breast MRI (bMRI) and 18 patients with bMRI findings only. Preoperative bMRI allowed staging the disease and localizing the lesion. In the operating theater, contrast medium was injected 1 minute before skin incision. After removal, surgical specimens were submitted to ex vivo MRI, performed using a dedicated surface coil and Spair inversion recovery sequences for suppression of fat signal intensity. All MRI enhancing lesions were completely included within the surgical specimen and visualized by ex vivo MRI. In the first 21 patients, bMRI was able to visualize branching margins or satellite nodules around the core lesion, and allowed for better staging of the surrounding in situ carcinoma; in the last 18 patients, eight of whom were breast cancer type 1 susceptibility protein (BRCA) mutation carriers, bMRI identified 12 malignant tumors, otherwise undetectable, that were all visualized by ex vivo MRI. This is the first description of a procedure that re-enhances breast lesions within a surgical specimen, demonstrating the surgical removal of nonpalpable breast lesions diagnosed only with bMRI. This new strategy reproduces the morphology and the entire extension of the primary lesion on the specimen, with potentially better local surgical control, reducing additional unplanned surgery.

Between 1982 and 1990, 321 elderly patients (range 70-92 years, median age 77) with operable breast cancer (T1 in 219, T2 in 77, T3 in one and T4b in 24 patients) and clinically uninvolved axillary nodes underwent surgery without axillary dissection and received adjuvant tamoxifen. All patients had surgery performed under local anaesthesia. Tamoxifen was given after surgery at the dose of 20 mg daily, indefinitely. With a median follow-up of 67 months (range 42-141), 17 patients developed local relapse, 14 ipsilateral axillary recurrence, five ipsilateral breast cancer, five contralateral breast cancer, 13 second primary and 23 developed distant metastases. The cumulative probability of developing a local, axillary and distant recurrence at 72 months was estimated to be 5.4%, 4.3% and 6.2%, respectively. Out of 244 patients who did not develop any relapse, 83 (25.8%) died from intercurrent disease. The 72 month relapse-free survival rate was 76%. This experience suggests that elderly patients with small tumours without clinical axillary involvement may be satisfactorily treated with conservative surgery and tamoxifen. The importance of axillary dissection is controversial owing to a high response rate to hormonal therapy and an increased death rate due to concomitant diseases.

Background. DNA ploidy and cell kinetics determined by flow-cytometric (FCM) analysis have provided relevant information on the natural history of breast cancer. These highly feasible and evaluable assays are particularly appropriate for small samples from fine-needle aspirates (FNA) to complement cytologic information for diagnosis of breast lesions. Methods. DNA content and the percentage of cells in the cell cycle phases were evaluated on FCM DNA histograms from 281 consecutive FNA of benign and malignant breast lesions. Results. FCM analysis was possible in 93% of FNA. Qualitative concordance in DNA content between FNA and surgical specimens was observed in 82% of the patients. Of the 145 aneuploid FNA, 144 (99%) were histologically diagnosed as carcinomas. The presence of only diploid clones was observed in 115 FNA: rapidly proliferating (S+G2M > 12%) diploid lesions proved to be histologically malignant in 67% of patients, and slowly proliferating diploid lesions were histologically benign in 79% of patients. False-positive results of ploidy and cell kinetics were observed in 1 and 10 patients, respectively. Of the 163 cancers evaluable for cytology and FCM, 158 were positive at cytology. The presence of aneuploid or of diploid rapidly proliferating clones in cytologically false-negative aspirates resulted in the detection of four additional cancers. Conclusions. Flow cytometric analysis of ploidy and cell kinetics on FNA could be a valuable tool complementary to cytology for breast cancer diagnosis.

The clinical-radiologic-cytologic triplet was used for diagnostic evaluation in 1708 women over 30 years old with a breast lump. All the lumps were subjected to surgery except for 258 cases in which clinical resolution took place within 1-2 months. Seven-hundred and ninety-three out of 1450 nodules removed were cancers. Sensitivity of the clinical, mammographic and cytologic examinations was 82%, 73% and 68%, respectively. It increased to 95% when they were as sociated. Specificity was 63%, 80% and 97%, respectively. The predictive value of positive results of the triple test was 100%. No patient with malignant cytology was subsequently shown to have benign disease. The systematic use of the triple test in solid breast lumps for the early detection of cancer is recommended as a routine procedure. However, participation of experienced radiologists and pathologists as well as physicians skilled in fine needle puncture is required.

BACKGROUND. In elderly patients with early breast cancer and a clinically clear axilla, axillary surgery, sentinel lymph node biopsy, and postoperative radiotherapy to the residual breast may not be necessary because of reduced life expectancy, effectiveness of hormone therapy in achieving long-term disease control, and generally favorable biologic behavior of breast cancer in elderly patients. METHODS. The authors followed 354 prospectively recruited women aged ≥70 years who had primary, operable breast cancer and no palpable axillary lymph nodes. All 354 women were treated with conservative surgery and adjuvant tamoxifen and without axillary dissection or postoperative radiotherapy. Women who had resection margins in tumor tissue were excluded. Endpoints were cumulative incidence of axillary disease, cumulative incidence of ipsilateral breast tumor recurrence (IBTR), and breast cancer mortality. RESULTS. After a median follow-up of 15 years (interquartile range, 14–17 years), the crude cumulative incidence was 4.2% (4% in pathologic T1 [pT1] tumors) for axillary disease, 8.3% (7.3% in pT1 tumors) for IBTR, and 17% for breast cancer mortality. Of the 268 patients who died during follow-up, 222 patients (83%) died from causes unrelated to breast cancer. CONCLUSIONS. Elderly patients with early breast cancer and no palpable axillary lymph nodes may be safely treated safety by conservative surgery without axillary dissection and without postoperative radiotherapy, provided that surgical margins are in tumor-free tissue and that hormone therapy is administered. Sentinel lymph node biopsy is also unnecessary because of the low cumulative incidence of axillary disease, and axillary surgery can be reserved for the small proportion of patients who later develop overt axillary disease. Cancer 2008. © 2007 American Cancer Society.

For many years, axillary dissection was part of the standard treatment of breast cancer following the pioneering studies by Halsted, early in the 20th century, which indicated that surgical clearance of the axilla resulted in better locoregional control and improved overall survival for the disease.1 Fisher et al2 were the first to publish data supporting the hypothesis that the resection of metastatic axillary nodes does not have a controlling influence on survival but may provide an indication of possible metastatic spread. Subsequent studies supported this hypothesis.3 Axillary dissection and more recently sentinel node biopsy4 are still considered important, not as treatments for breast cancer, but as a means of obtaining prognostic information for planning postsurgical systemic therapy. The affirmation of mammographic screening, resulting in increased detection of T1 cancers and a decrease in the proportion of cases with axillary lymph node involvement,5 strengthened the idea that axillary surgery may be safety omitted in most patients with early breast cancer. Furthermore, the prognostic role of axillary dissection is considered to have been superseded by biologic profiling of the primary tumor,6–8 which provides sufficiently reliable information for deciding if and what systemic treatments are necessary. In the elderly, the role of axillary dissection remains controversial, mainly because of a lack of data: high mortality for competing events, shorter life expectancy, and high response rate to hormone therapy have made it difficult to conduct appropriately powered randomized studies. Our previous prospective nonrandomized trial9 provided evidence that elderly patients with early stage breast cancer and no clinically evident axillary involvement can be effectively treated by quadrantectomy alone and tamoxifen: we found very low rates of locoregional failure in patients so treated, and no adverse effect on breast cancer mortality or overall survival. The present paper reports the results of a prospective randomized clinical trial on older patients with early stage breast cancer and clinically negative axillary nodes. Because of difficulties in recruiting older patients to clinical trials, we decided to randomize all eligible patients who consented to take part in the study over a 5-year study period. The main aim was to determine whether, in patients who received conservative breast surgery plus tamoxifen only, outcomes differed from those who also received axillary dissection. An additional aim was to estimate the incidence of axillary relapse in patients treated with surgery without axillary clearance.

A biological characterisation carried out on 14,007 primary breast cancers provided evidence in favour of a relation between advanced age and favourable features (positivity for oestrogen/progesterone receptors, low proliferative rate, absence of p53 accumulation, bcl-2 overexpression, diploid DNA content), showed a similar pattern of association between patho-biological variables regardless of patient age, and demonstrated a relation between biological variables and disease outcome in the elderly, comparable to that already reported for younger patients. In fact, oestrogen receptor and proliferative activity provided independent prognostic information either in node-negative or in node-positive tumours treated with radical or conservative surgery plus radiotherapy, alone or followed by adjuvant hormonal therapy. It would be thus reasonable to use biomarkers as a complement to clinico-pathological features in a 'risk-factor profile system' even for elderly patients, upon their validation in prospective studies and after assessing the cost-benefit of treatments planned on the basis of biological information.

BACKGROUND Axillary dissection in elderly patients with early-stage breast carcinoma who do not have palpable axillary lymph nodes is controversial because of the associated morbidity of the surgery, reduced life expectancy of the patients, and efficacy of hormone therapy in preventing recurrences and axillary events. METHODS The authors performed a retrospective analysis of 671 consecutive patients with breast carcinoma who were age ≥ 70 years and who underwent conservative breast surgery with axillary dissection (172 patients) or without axillary dissection (499 patients). Tamoxifen always was given. The effects of axillary dissection compared with no axillary dissection on breast carcinoma mortality and distant metastasis were analyzed using multiple proportional-hazards regression models. Because the assignment to axillary treatment was nonrandom, covariate adjustments were made for baseline variables that influenced the decision to perform axillary dissection and for prognostic factors. RESULTS The crude cumulative incidence curves for breast carcinoma mortality and distant metastasis did not appear to differ significantly between the two groups (P = 0.530 and P = 0.840, respectively). The crude cumulative incidences of axillary lymph node occurrence at 5 years and 10 years were 4.4% and 5.9%, respectively (3.1% and 4.1%, respectively, for patients with pT1 tumors). CONCLUSIONS Elderly patients with breast carcinoma who have no evidence of axillary lymph node involvement may be treated effectively with conservative surgery and tamoxifen. Immediate axillary dissection is not necessary but should be performed in the small percentage of patients who later develop overt axillary lymph node involvement. Cancer 2003;97:1156–63. © 2003 American Cancer Society. DOI 10.1002/cncr.11173

The predictive role of tumour proliferative rate and expression of p53, bcl-2 and bax proteins, alone and in association with tumour size, nodal involvement and oestrogen receptors (ER), was analysed on 145 elderly patients (≥70 years of age) with histologically assessed node-positive breast cancers treated with radical or conservative surgery plus radiotherapy followed by adjuvant tamoxifen for at least 1 year. The 7-year probability of relapse was significantly higher for patients with tumours rapidly proliferating (hazard ratio (HR) = 2.0, P = 0.01), overexpressing p53 (HR = 4.4, P = 0.0001), weakly or not exhibiting bcl-2 (HR = 1.9, P = 0.02), without ERs (HR = 3.4, P = 0.0001) or with ≥ 4 positive lymph nodes (HR = 2.3, P = 0.003) than for patients with tumours expressing the opposite patho-biological profile. Conversely, tumour size and bax expression failed to influence relapse-free survival. Adjustment for the duration of tamoxifen treatment did not change these findings. Oestrogen receptors, cell proliferation, p53 accumulation and bcl-2 expression were also predictive for overall survival. Within ER-positive tumours, cell proliferation, p53 accumulation, bcl-2 expression and lymph node involvement provided significant and independent information for relapse and, in association, identified subgroups of patients with relapse probabilities of 20% (low-risk group, exhibiting only one unfavourable factor) to 90% (high-risk group, exhibiting three unfavourable factors). Such data could represent the initial framework for a biologically tailored therapy even for elderly patients and highlight the importance of a patho-biological characterization of their breast cancers. © 2000 Cancer Research Campaign

In 83 elderly breast cancer patients, oestrogen and progesterone receptors (ER, PgR), pS2 and cathepsin D (CathD) were evaluated for their possible prognostic role on diseasefree survival (DFS). The biomarkers were determined on the same cytosol by using immunoradiometric assays, and the variables were considered on a continuous scale. Univariate analysis indicated a linear relationship between logarithmic hazard ratio (log(HR)) and the log(ER) and log(PgR) concentration, but a non-linear relationship between log(HR) and CathD. As regards pS2, there was no evidence of a relationship with log(HR). In multivariate analysis, log(ER) content did not have a significant prognostic role, whereas log(PgR) retained a significant prognostic role. As regards the predictive ability, log(PgR) was the best discriminator of outcome followed by CathD, whereas the contribution of log(ER) was negligible. In multivariate analysis, 2 models were considered: one with log(ER), pS2, CathD and the interaction between pS2 and CathD, and another with log(PgR), pS2, CathD and the interaction between pS2 and CathD. In the first model, log(ER) content did not have a significant prognostic role, whereas in the second model log(PgR) retained a significant prognostic role. Our findings indicate that the quantitative determination of pS2 and CathD, in addition to steroid receptors, on the same cytosolic fraction could be a complementary tool to describe all breast cancer patients rather than just the elderly and that the use of a continuous scale, instead of a simple dichotomous ‘‘status’’, may improve the biological information supplied by the variables. Int. J. Cancer (Pred. Oncol.) 79:305‐311, 1998. r 1998 Wiley-Liss, Inc.

A total of 606 consecutive patients with palpable breast lesions underwent physical examination, mammography, and fine-needle aspiration for cytologic and flow-cytometric (FCM) DNA analyses. FCM determinations included DNA ploidy and the fraction of cells in S + G2 + M phases. Aneuploid clones were considered indicative of malignancy; diploid, rapidly proliferating (S+G2+M>12%) clones were considered suggestive of malignancy; and diploid, slowly proliferating clones were considered indicative of benignancy. Sensitivity, specificity, and the predictive accuracy for positive or negative results of FCM information were 82%, 90%, 93.1% and 69.8%, respectively. These values were lower than those observed for the three conventional diagnostic assays owing to the presence of false-positive results (in 23 cases) or unassessable DNA plots (in 90 cases). FCM information alone detected five cases in which the other tests gave inconclusive results and in association to the conventional diagnostic triple test, increased the incidence of positive conclusive cases from 97.9% to 99.2%. However, further refinements are needed before this approach can be used as a routine diagnostic tool.

Between March 1982 and May 1989, 151 women with primary breast cancer ranging in age from 70 to 91 years (median 79), were treated with conservative surgical procedure followed by adjuvant tamoxifen. Surgery was performed under local anaesthesia without axillary node dissection. The median duration of follow-up was 60 months (range 36–124). There were six local, six ipsilateral axillary node and six distant relapses. Local recurrences were successfully managed with further surgery whereas axillary node relapses required radiotherapy in 3 cases, surgery in 2 cases and hormonal treatment in 1 case. 2 patients died of progression of disease and one of unrelated conditions. The 5-year relapse-free survival rate was 0.82. This treatment option in elderly patients yields an acceptable local control and reduces the risks of major surgery.

Between 1982 and 1988, 111 elderly women with breast cancer but without clinical involvement of the axillary lymph nodes underwent wide lumpectomy in a Day Hospital regimen at the National Cancer Institute of Milan. The patients ranged in age from 70 to 92 years (median, 79). An adjuvant treatment was carried out in all but 9 cases: tamoxifen only in 84 cases, tamoxifen plus radiotherapy in 6 cases, radiotherapy alone in 12 cases. The median duration of follow-up was 44 months (range, 30–109 months). Four patients (3.6%) were lost to follow-up. In the remaining 107 patients, 10 local-regional relapses (9.1 %) and 7 distant metastases (6.5 %) occurred. Six patients died from the disease, 14 from unrelated conditions. This retrospective study showed that selected elderly patients with breast cancers can be treated successfully under local anesthesia on an outpatient basis. The treatment guarantees local control of the disease, meets the favor of elderly women and consequently improves their quality of life.

The utility of fine needle aspiration (FNA) and physical examination for selecting patients with palpable thyroid nodules for surgery was evaluated in 795 consecutive cases. Surgery was performed in 216 patients based upon the cytological diagnosis and clinical criteria. Excluding 42 patients who were lost to follow-up, the remaining 537 were regularly followed up (range, 2–10 years). Cytological findings were classified as malignant, histologic control recommended (suspicious), follicular tumor, benign, and unsatisfactory. Thirty-six aspiration biopsies were positive for malignancy and the diagnosis was confirmed histologically in 34 of them. In 65 patients with final histological diagnosis of malignancy, cytology was positive in 34, suspicious in 20, benign in 3 cases, and unsatisfactory in 8. All patients with cytological diagnosis of follicular tumor had a benign lesion at histology. There were two false positive and three false negative cytological results among the 216 histologically confirmed cases. Excluding unsatisfactory specimen sensitivity, specificity and the predictive value for a positive and a negative result were respectively 95%, 97.5%, 94.5%, and 97%. We conclude that FNA is a very reliable diagnostic test in the evaluation of thyroid nodules and is the best guidance in addition to clinical criteria for selecting patients to be submitted to surgery. © 1992 Wiley-Liss, Inc.

The aim of the study was to ascertain the reliability of a Doppler signal in the diagnosis of breast cancer. Computerized blood flow analysis was performed on 117 patients who presented with a breast lump at the Division of Diagnostic Oncology of the Istituto Nazionale Tumori of Milan. The values of systolic peak and diastolic frequency were evaluated in relation to the histologic diagnosis. Ten patients had a spontaneous regression of the lump and were excluded from the study. The number of evaluable cases with histologic confirmation was 107: 69 carcinomas and 38 benign lesions. Systolic peak values for the 69 carcinomas ranged from 1500 to 7400 Hz, with a mean value of 3243.4 Hz; diastolic frequency ranged from 200 to 3700 Hz, with mean value of 1413.9 Hz. No diagnostic signals were found in 4 breast cancers (false negatives). Twenty-three of 38 benign lesions (60.5 %) and 65 of 69 malignant nodes (94.2 %) were correctly diagnosed. The Doppler signal with computerized spectral analysis in addition to more specific ultrasonographic parameters could be considered a useful tool in the diagnosis of breast cancer.