Progesterone signalling in breast cancer: a neglected hormone coming into the limelight

Brisken, Cathrin

doi:10.1038/nrc3518

Cited by 213 publications

(178 citation statements)

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“…2). It is important to note, however, that the progesterone receptor, under intense investigation in breast cancer 21 , may also be involved in cancer of non-reproductive organs, like what recently reported for lung NSCLC 22 and colon cancer 23 . a) Stem cell renewal : Specific ablation of estrogen receptor α, β and androgen receptor affects homeostasis and/or regeneration of organs unrelated to reproductive functions, such as lung 24, , colon 25 and skin [26][27][28] .…”

Section: Introduction (Epidemiology)mentioning

confidence: 77%

Sexual dimorphism in cancer

et al. 2016

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The incidence of many cancer types is significantly higher in the male than female populations, with associated differences in survival. Occupational and/or behavioral factors are well known underlying determinants. However, cellular/molecular differences between the two sexes are also likely to be important. We are focusing here on the complex interplay that sexual hormones and sex chromosomes can have in intrinsic control of cancer initiating cell populations, tumor microenvironment and systemic determinants of cancer development like the immune system and metabolism. A better appreciation of these differences between the two sexes could be of substantial value for cancer prevention as well as treatment.3 Introduction (Epidemiology)

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Section: Introduction (Epidemiology)mentioning

confidence: 77%

Sexual dimorphism in cancer

et al. 2016

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“…The PgR is synthesized by tumor cells following stimulation by estrogens through interaction with the ER. The ER pathway targets PgR, the presence of which reflects a functional ER pathway (37,38). In theory, PgR may be a better indicator of hormonal dependence.…”

Section: Discussionmentioning

confidence: 99%

Prognostic impact of progesterone receptor status combined with body mass index in breast cancer patients treated with adjuvant aromatase inhibitor

et al. 2015

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Abstract.Aromatase inhibitors have played a central role in endocrine therapy for the treatment of estrogen receptor (ER)-positive breast cancer in postmenopausal patients. However, prognostic factors for recurrence following such treatment have not been identified. The current study aimed to validate the prognostic value of endocrine-related progesterone receptor (PgR) status combined with body mass index (BMI). Among 659 consecutive patients with primary breast cancer who underwent curative surgery between 2002 and 2012, 184 postmenopausal patients with ER-positive (ER+) and human epidermal growth factor receptor type 2-negative (HER2-) breast cancer who were treated with adjuvant aromatase inhibitor therapy were assessed. The patients were assigned to groups based on BMI, according to the WHO cut-off value: ≥25 kg/m 2 (high, H) or <25 kg/m 2 (low, L). Positive nodal status, negative PgR status, BMI-H and a high Ki-67 labeling index (≥20%) were found to be significantly associated with a short recurrence-free interval (RFI) upon univariate analysis (P=0.048, 0.007, 0.027, and 0.012, respectively). The patients were further grouped based on their combined PgR/BMI status. The RFI was significantly shorter in the PgR-and/or BMI-H group compared with that of the PgR+/BMI-L group (P=0.012). Multivariate analysis revealed PgR-tumors and/or BMI-H and positive nodal status to be independent prognostic factors (P=0.012 and 0.020, respectively). The present findings indicate that PgR/BMI status may serve as a practical tool in the management of ER+ and HER2-breast cancer in patients treated with adjuvant aromatase inhibitors. IntroductionAromatase inhibitors have been widely administered as adjuvant treatment for hormone receptor-positive breast cancer in postmenopausal women. The results of recent clinical trials have demonstrated that third-generation aromatase inhibitors, including anastrozole, letrozole and exemestane, are more effective than tamoxifen in treating early stage or metastatic breast cancer in postmenopausal women (1). Thus, aromatase inhibitors are now considered to be the gold standard of endocrine therapy for such patients in adjuvant and metastatic settings (2,3). Characterization of the risk of recurrence for patients who receive aromatase inhibitors is important for selecting appropriate treatment. However, factors that can predict the outcomes of aromatase inhibitor treatment remain unknown.A number of studies have investigated tumor biomarkers that indicated differential benefit from aromatase inhibitors versus tamoxifen in patients with early breast cancer (4-6). Such biomarkers included the conventional factors, estrogen receptor (ER), progesterone receptor (PgR), human epidermal growth factor receptor type 2 (HER2) and Ki-67, and did not identify patients who derived a differential relative benefit from aromatase inhibitors over tamoxifen. Expression of the PgR gene is thought to largely depend on an intact ER signaling pathway, and the expression of PgR is associated with endocrine responsiv...

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“…The activity of PgR is regulated by ligand binding, as well as phosphorylation by among others MAPK, CDK2/cyclin A and CK2. In general, sustained high levels of oestrogen and progesterone are predisposing for breast cancer, but as clinical markers ER and PgR are associated with low grade tumours, a favourable short-term prognosis and response to endocrine therapies [32]. Alterations in the balance between PgRA and PgRB have been observed in tumour cells, and a high PgRA/PgRB has been associated with poor prognosis and less response to endocrine therapies [31].…”

Section: B)mentioning

confidence: 99%

Clinical potential of the mTOR effectors S6K1, S6K2 and 4EBP1 in breast cancer

Karlsson¹

2014

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FÖRORD OCH FÖRFATTARENS TACKBröstcancer är i dag en av våra största folksjukdomar. Tack vare intensiv forskning och klinisk utveckling överlever nu allt fler denna sjukdom, men ännu behöver mycket mer göras. Jag är mycket tacksam över att ha fått möjlighet att delta i denna kamp mot cancer under dessa år som denna avhandling sammanställts, och förhoppningen är att denna studie tillsammans med andra studier, kan vara en användbar pusselbit och ett steg i rätt riktning. Jag vill här rikta ett varmt tack till alla som gjort denna resa möjlig:Drabbade patienter och anhöriga, klinisk och teknisk personal, samt bidragsgivare och alla som stödjer dessa arbeten runt om i vårt land. Patienters aktiva deltagande i kliniska studier och vävnadsdonation möjliggör forskningens fortsatta arbete och hjälper många.Avd. för Onkologi vid Hälsouniversitetet, Linköping och dess ämnesföreträdare Charlotta Dabrosin och samordnare Chatarina Malm, för möjligheten att göra min forskarutbildning på avdelningen.Olle Stål, min huvudhandledare under forskarutbildningen, som gav mig chansen att göra denna resa. Genom din stora ödmjukhet har du visat att det går att driva forskning "med hjärtat". Du är min förebild i forskningsvärlden.Anna-Lotta Hallbeck, min bihandledare, som varit vår länk in till bröstcancerkliniken. Varje möte med dig är enormt lärorikt, och ger perspektiv.Patrik Lundström, min bihandledare, som gett vårt projekt en ny vinkel med djupare biokemisk och bioteknisk kunskap. Tack för ett gott samarbete, inga projekt är omöjliga! Alla nuvarande och tidigare vänner och kollegor på KEF, Cellbiologen och Valla; stort tack för alla goda samarbeten, för all hjälp och för att ni skapat en kreativ och hemtrevlig forskningsmiljö, lycka till med ert fortsatta arbete, med hopp om fortsatta samarbeten.Alla examensarbetare och medförfattare som jag fått förmånen att jobba tillsammans med, det har varit väldigt givande och lärorikt.Studenter och handledarkollegor i basgrupper och under alla labbar, er nyfikenhet har varit en stor inspirationskälla.Tidigare lärare under alla år i skolan, som med er entusiasm väckt mitt intresse för naturvetenskap och biomedicin, däribland Biomedicinska forskarskolan 2006-2007. Min familj och mina vänner som varit ett ovärderligt stöd under resan. Jag är övertygad om att omtanke om varandra, att vara ute i naturen och att musicera tillsammans är den bästa hjälpen för allt, inklusive att bearbeta forskningsproblem. Tumörsjukdomar, för kvinnor främst bröst-och lungcancer, utgör en av de främsta dödsorsakerna i västvärlden i dag. Tack vare utveckling av metoder för diagnos och behandling, liksom upptäckt på allt tidigare stadium har prognosen för bröstcancerpatienter förbättrats radikalt de senaste 25-30 åren. Dock diagnosticeras i Sverige ca 8000 nya fall av bröstcancer varje år, och omkring 1500 kvinnor dör av sjukdomen. Elin Karlsson, Adelöv 2014Ett stort problem är att brösttumörer är väldigt olikartade, och kanske egentligen borde betraktas som flera olika sjukdomar. Ett mål med dagens forskning är därfö...

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Progesterone signalling in breast cancer: a neglected hormone coming into the limelight

Cited by 213 publications

References 96 publications

Sexual dimorphism in cancer

Sexual dimorphism in cancer

Prognostic impact of progesterone receptor status combined with body mass index in breast cancer patients treated with adjuvant aromatase inhibitor

Clinical potential of the mTOR effectors S6K1, S6K2 and 4EBP1 in breast cancer

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