Breast cancer biological subtypes and protein expression predict for the preferential distant metastasis sites: a nationwide cohort study

Introduction Some molecular subtypes of breast cancer have preferential sites of distant relapse. The protein expression pattern of the primary tumor may influence the first distant metastasis site. Methods We identified from the files of the Finnish Cancer Registry patients diagnosed with breast cancer in five geographical regions Finland in 1991-1992, reviewed the hospital case records, and collected primary tumor tissue. Out of the 2,032 cases identified, 234 developed distant metastases after a median follow-up time of 2.7 years and had the first metastatic site documented (a total of 321 sites). Primary tumor microarray (TMA) cores were analyzed for 17 proteins using immunohistochemistry and for erbB2 using chromogenic in situ hybridization, and their associations with the first metastasis site were examined. The cancers were classified into luminal A, luminal B, HER2+ enriched, basal-like or non-expressor subtypes. Results A total of 3,886 TMA cores were analyzed. Luminal A cancers had a propensity to give rise first to bone metastases, HER2-enriched cancers to liver and lung metastases, and basal type cancers to liver and brain metastases. Primary tumors that gave first rise to bone metastases expressed frequently estrogen receptor (ER) and SNAI1 (SNAIL) and rarely COX2 and HER2, tumors with first metastases in the liver expressed infrequently SNAI1, those with lung metastases expressed frequently the epidermal growth factor receptor (EGFR), cytokeratin-5 (CK5) and HER2, and infrequently progesterone receptor (PgR), tumors with early skin metastases expressed infrequently E-cadherin, and breast tumors with first metastases in the brain expressed nestin, prominin-1 and CK5 and infrequently ER and PgR. Conclusions Breast tumor biological subtypes have a tendency to give rise to first distant metastases at certain body sites. Several primary tumor proteins were associated with homing of breast cancer cells.BioMed Central Open acces

Long-term prognosis of breast cancer detected by mammography screening or other methods

Introduction Previous studies on breast cancer have shown that patients whose tumors are detected by mammography screening have a more favorable survival. However, little is known about the long-term prognostic impact of screen-detection. The purpose of the current study was to compare breast cancer-specific long-term survival between patients whose tumors were detected in mammography screening and those detected by other methods. Methods Breast cancer patients diagnosed within five specified geographical areas in Finland in 1991-92 were identified (n=2,936). Detailed clinical, treatment and outcome data as well as tissue samples were collected. Women with in situ carcinoma, distant metastases at the primary diagnosis and women who were not operated were excluded. Main analyses were made with exclusions of patients with other malignancy or contralateral breast cancer followed by to sensitivity analyses with different exclusion criterias. Median follow-up time was 15.4 years. Univariate and multivariate analysis of breast cancer-specific survival were performed. Results Of patients included in the main analyses (n=1,884) 22% (n=408) were screen-detected and 78% (n=1,476) were detected by other methods. Breast cancer-specific 15-year survival was 86% for patients with screen-detected cancer and 66% for patients diagnosed by other methods (p<0.0001, HR=2.91). Similar differences in survival were also observed in women at screening age (50-69 years) as well as in clinically important subgroups, such as patients with small tumors ([less than or equal to]1cm in diameter) and without nodal involvement (N0). Women with breast cancer diagnosed by screening mammography had a more favorable prognosis compared to those diagnosed outside of screening program following adjustments according to patient age, tumor size, axillary lymph node status, histological grade and hormone receptor status. Significant differences in the risk of having future contralateral breast cancer according to method of detection was not observed . Conclusions Breast cancer detection in mammography screening is an independent prognostic factor in breast cancer and is associated with a more favorable survival also in long-term follow-up.BioMed Central open acces

Sosiaaliset verkostot ja vastasairastuneiden syöpäpotilaiden elämänlaatu

Tiivistelmä Johdanto: Sosiaaliset verkostot ovat tärkeitä hyvinvointiresursseja. Tutkimme vastasairastuneiden syöpäpotilaiden sosiaalisten verkostojen yhteyttä heidän elämänlaatuunsa. Menetelmät: Mittasimme Oulun yliopistollisen sairaalan (OYS) syöpätautien klinikkaan hoitoon tulleiden 224 rintasyöpä- ja 150 eturauhassyöpäpotilaan sosiaalisia verkostoja (puoliso, perhe, omaiset, ystävät, tuttavat, muut syöpäpotilaat, hoitohenkilökunta, työyhteisöjen jäsenet, osallistuminen harrastus- tai järjestötoimintaan) 2–5 kuukautta diagnoosin jälkeen. Kysyimme, keille potilaat olivat kertoneet syövästään ja mittasimme heidän terveyteensä liittyvää elämänlaatuaan. Tuloksett: Potilailla oli yleensä runsaasti ihmissuhteita, ja he olivat kertoneet näille syövästään. Lähiverkostojen olemassaolo ja henkilömäärä (puoliso, aikuiset lapset, rintasyöpäpotilailla myös ystävät) olivat yhteydessä huonompaan hyvinvointiin. Sen sijaan tätä kaukaisemmat ihmissuhteet (lasten puolisot, puolison vanhemmat, kaukaisemmat sukulaiset ja muut verkostot, eturauhassyöpäpotilailla myös ystävät) olivat yhteydessä parempaan hyvinvointiin. Päätelmät:. Lähiverkostojen yhteys huonompaan hyvinvointiin saattaa selittyä sillä, että vastasairastuneiden syöpäpotilaiden hyvinvointia kuormittaa huoli läheisimpien hyvinvoinnista.Abstract Background: Social relationships are important resources for health and well-being. These are derived from an individual’s social environment and comprise of social interactions between persons. Social resources have been investigated as social networks, social support, and social capital. Social networks act as sources of social support and are the origins of social capital. Social networks consist of social ties between individuals and groups. We explored newly diagnosed cancer patients’ social networks and investigated their association with the patients’ well-being. Methods: We evaluated breast cancer (n=224) and prostate cancer (n=150) patients’ social networks (existence and person numbers) in the following subnetworks: spouse/partner; family; close relatives, close friends; acquaintances; others with cancer; work community; health professionals; participation (religious, hobby, civic participation) at 2–5 months after diagnosis, and whether they had discussed their cancer with these ties. We measured health-related quality of life and depressive symptoms of the patients and investigated the predictors of these with multivariate analyses. Results: The patients had usually multiple social relationships and had told them about their cancer. Contrary to what had been expected, the strongest ties (spouse/partner and adult children, in breast cancer also friends) were associated with poorer well-being. However, weak ties (spouses of adult children, spouse’s parents, more distant relatives, and extensive social contacts (in breast cancer patients also participation and in prostate cancer patients also friends) predicted better well-being. Conclusions: The association between social networks and well-being depended on the strength of the social subnetwork. Contrary to theories on social support, the strongest ties, i.e., the next of kin, predicted poorer wellbeing. Only weak ties acted as well-being resources. Because of acting as caregivers or worrying about wellbeing of their loved ones, patients with strong social ties may be more burdened and may thus need extra attention

Interim and end-of-treatment PET-CT suffers from high false-positive rates in DLBCL:biopsy is needed prior to treatment decisions

Abstract The application of positron emission tomography (PET)-computed tomography (CT) in treatment response evaluation has increased in diffuse large B-cell lymphoma (DLBCL), although its predictive value is controversial. We retrospectively analyzed the rate of false-positive PET-CTs performed as interim (n = 94) and end-of-treatment (n = 8) assessments among 102 DLBCL patients treated during 2010–2017 at Oulu University Hospital. In PET-CT Deauville score ≥4 was regarded as positive. A biopsy was performed on 35 patients, and vital lymphoma tissue was detected from nine patients. Positive biopsy findings were associated with poor disease outcomes in this study. This difference was statistically significant: 2-year failure-free survival (FFS) was 44% in patients with a positive biopsy versus 83% for those with a negative biopsy (p = 0.003). The corresponding overall survival (OS) rates were 53% versus 95% (p = 0.010). In the multivariate analyses, a negative biopsy was an independent protective factor in FFS (Hazard Ratio (HR) 0.093 (95% confidence interval [CI] 0.017–0.511); p = 0.006) unrelated to the International Prognostic Index (IPI) (HR 1.139 [95% CI 0.237–5.474] p = 0.871) or stage (HR 1.365 [95% CI 0.138–13.470]; p = 0.790). There was no statistically significant difference in OS according to the PET results, but the FFS rate was significantly higher in patients with a negative PET. The value of PET-CT as an evaluation method suffers from a high false-positive rate, and it is inadequate alone for the justification of treatment decisions. Biopsy results provide more reliable prognostic information for the evaluation of treatment response and outcome and should be used to assess patients with positive PET-CT scans

Significance of bulky mass and residual tumor:Treated with or without consolidative radiotherapy—To the risk of relapse in DLBCL patients

Abstract Bulky and residual tumor are considered to increase the risk of relapse in diffuse large B‐cell lymphoma (DLBCL) patients. Radiotherapy is conventionally used to reduce the risk, but the evidence is controversial. We performed a retrospective analysis to evaluate the significance of bulky and residual tumor treated with or without radiotherapy in DLBCL patients. We analyzed 312 DLBCL patients treated from 2010‐2017 in Oulu University Hospital. A bulky tumor was detected in 123 patients and 55 of these patients (44.3%) received consolidative radiation therapy (RT) to the bulky tumor. Residual tumor meeting the required criteria was found in 138 (39.3%) patients, and 65 (45.5%) of these patients received consolidative RT to the site of residual tumor. iPET‐CT scans were performed in 102 patients. In multivariate analyses, bulky was an independent risk factor in limited stage patients in progression free survival (HR 6.43 [95%CI 1.609‐25.710]; P = .008) not related to International prognostic index (HR 1.35 [95% CI 0.256‐7.124]; P = .724) or age (HR 1.62 [95% CI 0.468‐5.638]; P = .445). This was not seen in advanced stage patients or in patients with residual tumor. Radiotherapy to the bulky or residual tumor was not able to improve the long‐term PFS of patients. In this study, it appears that performing iPET is the most convincing method in improving evaluation and in finding patients with increased risk of relapse. Evidently, patients with negative iPET will not benefit from including RT in the treatment after metabolic complete response (CR), and patients with primary refractory disease are most likely in the group of positive iPET

Sosiaalisten resurssien vaikutus hyvinvointiin ja terveyteen:sairausspesifi sosiaalinen pääoma

Tiivistelmä Sosiaaliset eli ihmisten väliset suhteet ja terveys ovat olleet pitkään tieteellisen tutkimuksen kohteena, mutta sosiaalisen pääoman käsite nousi terveystutkimuksessa esiin vasta 1990-luvulla. Sosiaalista pääomaa tutkitaan usean eri tieteenalan piirissä, mutta määritelmästä ei olla yksimielisiä; sen kuitenkin ajatellaan tuottavan hyötyjä, muun muassa parempaa hyvinvointia ja terveyttä. Sosiaalinen pääoma koostuu useasta eri alakäsitteestä ja yleensä se tarkoittaa ihmissuhteista saatavia resursseja, jotka koostuvat sosiaalisista verkostoista (rakenne) sekä niissä jaetuista arvoista, uskomuksista, käsityksistä ja asenteista (sisältö), kuten luottamus ja vastavuoroisuus. Sosiaalista pääomaa tutkitaan sekä yksilön ominaisuutena (kuinka yksilöt hyötyvät) että yhteisön ominaisuutena (miksi jotkut yhteisöt pärjäävät toisia paremmin). Yksilötason sosiaalista pääomaa mitataan yksilön sosiaalisina verkostoina ja niiden sisältönä, mm. luottamuksena. Yhteisöllisessä sosiaalisessa pääomassa taas mitataan yhteisöjen, esim. alueiden, ominaisuuksia. Kehittämämme uuden teoreettisen mallin mukaan vakavaan tai pitkäaikaiseen somaattiseen sairauteen sairastuneiden sosiaalista pääomaa tutkittaessa yksilötason sosiaalinen pääoma tulee jakaa yleiseen ja tilannesidonnaiseen eli sairausspesifiin pääomaan. Jälkimmäisen sosiaalisen pääoman rakenteen muodostavat ne sosiaaliset verkostot, joiden kanssa henkilö on ollut vuorovaikutuksessa sairautensa johdosta. Se muodostuu henkilöllä jo ennen sairautta olleen sosiaalisen pääoman pohjalta sekä niistä sosiaalisista verkostoista ja niiden sisällöstä, jotka syntyvät sairauden ja sen hoitojen seurauksena. Sairastumisen aiheuttama muutos sosiaalisissa verkostoissa johtaa sairauspesifin sosiaalisen pääomaan muodostumiseen. Selkeytämme mallissamme myös eri luottamuskäsitteiden vaikutusta sosiaalisen pääoman osatekijöinä

Treatment of diffuse large B‐cell lymphoma in elderly patients:replacing doxorubicin with either epirubicin or etoposide (VP‐16)

Abstract Diffuse large B‐cell lymphoma (DLBCL) is the most common type of lymphoma. The standard therapy for DLBCL is R‐CHOP. The current 5‐year overall survival is 60% to 70% using standard frontline therapy. However, the use of doxorubicin and its cardiotoxicity is a major clinical problem and preexisting cardiac disease may prevent the use of doxorubicin. Age greater than 65 years is a significant risk factor for anthracycline‐induced cardiotoxicity, and therefore, the use of R‐CHOP is often withheld from elderly patients. The feasibility of replacing doxorubicin with either epirubicin or etoposide in patients who have risk factors for heart complications is analyzed here. Clinical data of 223 DLBCL patients were retrospectively collected from hospital records. Fifty‐five patients were treated with R‐CHOP, 105 with R‐CIOP (epirubicin instead of doxorubicin), 17 with R‐CEOP (etoposide instead of doxorubicin), and 31 with R‐CHOEP. Matched‐pair analysis was carried out between 30 patients treated with R‐CEOP and R‐CHOP. For all patients, the 2‐year progression‐free survival (PFS) was 73.6%. In patients treated with R‐CHOP, the 2‐year PFS was 84.2%, with R‐CIOP 64.4%, with R‐CEOP 87.7%, and with R‐CHOEP 83.2%. In matched‐pair analysis, the 2‐year PFS was 92.3% with R‐CHOP and 86.2% with R‐CEOP. The 2‐year disease specific survival was 100% with R‐CHOP and 86.2% with R‐CEOP. In conclusion, R‐CEOP offers reasonable PFS and disease specific survival in the treatment of DLBCL and good disease control can be achieved in elderly patients. Elderly patients with impaired cardiac function could benefit from the use of R‐CEOP instead of R‐CHOP. The results with R‐CIOP were unsatisfactory, and we do not recommend using this protocol in elderly patients with cardiac disease

Syöpään sairastuneiden sosiaaliset verkostot diagnoosivaiheessa ja seuraavien kolmen vuoden aikana

Abstrakti Sosiaaliset verkostot ovat yksilöiden ja ryhmien välisiä sidoksia, jotka kuvaavat sosiaalisiin suhteisiin ja aktiviteetteihin osallistumista. Sosiaaliset verkostot edistävät terveyttä, esimerkiksi syöpäpotilailla verkostojen on todettu olevan yhteydessä hyvinvointiin ja vähentyneeseen kuolleisuuteen. Mittasimme Oulun ylipistolliseen sairaalaan (OYS) hoitoon tulleiden uusien rintasyöpä- (n=222) ja lymfoomapotilaiden (n=102) sosiaalisia verkostoja 2–5 kuukautta diagnoosin jälkeen sekä 9, 18 ja 36 kuukauden kuluttua. Kysyimme verkostojen henkilömäärää ja kuinka monen kanssa potilas oli puhunut syövästään seuraavissa osaverkostoissa: puoliso, perhe, lähipiiriin kuuluvat omaiset (aikuiset lapset perheineen, omat/puolison vanhemmat, omat/puolison sisarukset, tätä kaukaisemmat sukulaiset), läheiset ystävät, tuttavat, muut syöpäpotilaat, syöpää hoitaneet henkilöt, työyhteisö, muut hoitosuhteet, osallistuminen (uskonnollinen yhteisö, harrastukset, järjestötoiminta). Alkuvaiheessa lähes 90 %:lla oli puoliso/kumppani, neljäsosalla kotona asuvia lapsia ja kaikilla joitakin lähipiiriin kuuluvia omaisia. Kolmella neljästä oli aikuisia lapsia perheineen (nuoremmilla useammin omia/puolison vanhempia, vanhemmilla aikuisia lapsia puolisoineen ja lastenlapsia) ja lähes kaikilla sisaruksia. Useimmilla oli ystäviä. Em. lähiverkostot olivat tyypillisesti laajoja ja kaikille oli yleensä puhuttu syövästä. Neljä viidestä oli jo alkuvaiheessa puhunut tuttaville ja muille syöpään sairastuneille. Työssä olevat olivat yleensä puhuneet työyhteisössään. Seurannassa jotkin osaverkostot harvinaistuivat ja supistuivat hiukan, rintasyöpäpotilailla enemmän kuin lymfoomapotilailla, mutta lähipiiriin kuuluvien kaukaisempien sukulaisten ja ystävien määrä suureni alkuvaiheen ja yhdeksän kuukauden välillä. Muiden syöpäpotilaiden määrä lisääntyi koko ajan. Sairastuneilla oli paljon ja laajoja sosiaalisia verkostoja, joissa varsinkin läheisille oli puhuttu syövästä. Lähiverkostot olivat eri-ikäisillä erilaisia. Sairastumisen jälkeen lähipiiriin tuli lisää sukulaisia ja ystäviä, ja verkostoihin liittyi kanssapotilaita ja hoitoon osallistuvia. Vaikka osaverkostot saattoivat seurannassa vähentyä, tätä tapahtui hyvän ennusteen omaavassa syövässä (rintasyöpä) enemmän kuin vakavammassa (lymfooma). Tulkitsemme, että jälkimmäisillä oli suurempi tarve ylläpitää tukea antavia ihmissuhteita

Case report: chemotherapy in conjunction with blood–brain barrier disruption for a patient with germ cell tumor with multiple brain metastases

Clinical practice points Testicular cancer with brain metastases is related to poor prognosis because the penetration of chemotherapeutic agents is decreased by the blood–brain barrier. The standard treatment of brain metastases—whole brain radiation therapy combined with chemotherapy—is related to a limited increase in survival and considerable deleterious cognitive effects. The blood–brain barrier can be transiently disrupted using hyperosmolar intra-arterial mannitol injection. When combined with intra-arterial chemotherapy, therapeutic intratumoral concentrations can be attained. In experienced centers, blood–brain barrier disruption therapy is relatively safe with a low incidence of catheter-related complications. Blood–brain barrier disruption therapy is a promising treatment modality for brain metastases as an alternative to whole brain radiation therapy

Low Rap1-interacting factor 1 and sirtuin 6 expression predict poor outcome in radiotherapy-treated Hodgkin lymphoma patients

Abstract Sirtuins (SIRTs) are a family of histone deacetylases, which widely regulate cellular metabolism and are also involved in DNA repair. Rap1-interacting factor 1 (Rif1) and O⁶-alkylguanine DNA alkyltransferase (MGMT) are DNA-repair enzymes, which may potentially be involved in resistance to treatment of classical Hodgkin lymphoma (HL). We assessed the expression levels of (previously unstudied) SIRT1, SIRT4, SIRT6, Rif1, and MGMT immunohistochemically in 85 patients with untreated classical HL. Aberrant distributions of SIRT1, SIRT4, and SIRT6 were detected in Hodgkin neoplastic Reed–Sternberg (RS) cells compared with reactive elements. Low-level expression of both Rif1 and SIRT6 predicted dismal relapse-free survival in radiotherapy-treated patients (multivariate analysis; HR 8.521; 95% CI 1.714–42.358; p = .0088). Expression levels of SIRT1, 4, and 6 were abnormally distributed in RS cells, suggesting a putative role of aberrant acetylation in classical HL carcinogenesis. Rif1 and SIRT6 may also have substantial prognostic and even predictive roles in classical HL