Article
Medicine, General & Internal
Gabriel N. Hortobagyi, Salomon M. Stemmer, Howard A. Burris, Yoon-Sim Yap, Gabe S. Sonke, Lowell Hart, Mario Campone, Katarina Petrakova, Eric P. Winer, Wolfgang Janni, Pierfranco Conte, David A. Cameron, Fabrice Andre, Carlos L. Arteaga, Juan P. Zarate, Arunava Chakravartty, Tetiana Taran, Fabienne Le Gac, Paolo Serra, Joyce O'Shaughnessy
Summary: First-line therapy with ribociclib plus letrozole showed a significant overall survival benefit as compared with placebo plus letrozole in patients with HR-positive, HER2-negative advanced breast cancer. Median overall survival was more than 12 months longer with ribociclib than with placebo.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Oncology
Igor Makhlin, Nicholas P. McAndrew, E. Paul Wileyto, Amy S. Clark, Robin Holmes, Lisa N. Bottalico, Clementina Mesaros, Ian A. Blair, Grace R. Jeschke, Kevin R. Fox, Susan M. Domchek, Jennifer M. Matro, Angela R. Bradbury, Michael D. Feldman, Elizabeth O. Hexner, Jacqueline F. Bromberg, Angela DeMichele
Summary: Circulating IL-6, an activator of JAK/STAT signaling, is associated with poor prognosis and AI resistance in HR+ breast cancer. A phase 2 trial combining Ruxolitinib and exemestane in AI-resistant patients showed minimal activity but good safety. These findings highlight the need for more potent and specific inflammation-targeting therapies in MBC.
Article
Endocrinology & Metabolism
Bjorn-Erik Bertelsen, Kristin Viste, Thomas Helland, Magnus Hagland, Havard Soiland, Jurgen Geisler, Tone Hoel Lende, Per Eystein Lonning, Jorn Sagen, Gunnar Mellgren, Bjorg Almas
Summary: This study developed a liquid chromatography-tandem mass spectrometry (MS/MS) method for simultaneous measurement of serum levels of third-generation aromatase inhibitors (AIs) and ultra-low levels of estrogens. The method is highly valuable for studying drug efficacy and compliance.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Oncology
Edoardo Isnaldi, Francois Richard, Maxim De Schepper, Sophia Leduc, Marion Maetens, Tatjana Geukens, Karen Van Baelen, Ha-Linh Nguyen, Ghizlane Rouas, Gabriele Zoppoli, Fatima Cardoso, Christos Sotiriou, Denis Larsimont, Giuseppe Floris, Elia Biganzoli, Christine Desmedt
Summary: The impact of adiposity on the efficacy of endocrine treatment in patients with estrogen receptor positive breast cancer was investigated retrospectively. It was found that obesity and larger adipocyte diameter are associated with a higher likelihood of anti-proliferative response in neoadjuvant treatment.
Article
Oncology
Davide Serrano, Sara Gandini, Parjhitham Thomas, Katherine D. Crew, Nagi B. Kumar, Lana A. Vornik, J. Jack Lee, Paolo Veronesi, Giuseppe Viale, Aliana Guerrieri-Gonzaga, Matteo Lazzeroni, Harriet Johansson, Mauro D'Amico, Flavio Guasone, Stefano Spinaci, Bjorn-Erik Bertelsen, Gunnar Mellgren, Isabelle Bedrosian, Diane Weber, Tawana Castile, Eileen Dimond, Brandy M. Heckman-Stoddard, Eva Szabo, Powel H. Brown, Andrea DeCensi, Bernardo Bonanni
Summary: This study compared different dosing schedules of exemestane, an aromatase inhibitor, in patients with breast cancer. The results showed that a 25mg dose taken three times weekly was as effective as a daily dose in decreasing serum estradiol levels, suggesting that this alternative schedule warrants further investigation.
Article
Biochemistry & Molecular Biology
Beata Filip-Psurska, Mateusz Psurski, Artur Anisiewicz, Patrycja Libako, Ewa Zbrojewicz, Magdalena Maciejewska, Michal Chodynski, Andrzej Kutner, Joanna Wietrzyk
Summary: Both the vitamin D active metabolite and synthetic analog can regulate the growth of not only estrogen receptor-positive cells, but also hormone-independent cancer cells, while combined with An, PRI-2191 and PRI-2205 significantly inhibit the tumor growth of MCF-7 cells. The potentiation of the antitumor activity in combined treatment of MCF-7 tumor-bearing mice is related to the reduced activity of aromatase and regulation of the expression of estrogen receptor ER alpha and VDR.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Oncology
Lucia Del Mastro, Mauro Mansutti, Giancarlo Bisagni, Riccardo Ponzone, Antonio Durando, Laura Amaducci, Enrico Campadelli, Francesco Cognetti, Antonio Frassoldati, Andrea Michelotti, Silvia Mura, Ylenia Urracci, Giovanni Sanna, Stefania Gori, Sabino De Placido, Ornella Garrone, Alessandra Fabi, Carla Barone, Stefano Tamberi, Claudia Bighin, Fabio Puglisi, Gabriella Moretti, Grazia Arpino, Alberto Ballestrero, Francesca Poggio, Matteo Lambertini, Filippo Montemurro, Paolo Bruzzi
Summary: The study showed that extending letrozole treatment to 5 years in postmenopausal patients with breast cancer who had received 2-3 years of tamoxifen resulted in a significant improvement in disease-free survival compared to the standard 2-3 years of letrozole treatment.
Review
Oncology
Melika Shirdarreh, Rossanna C. Pezo
Summary: Studies have shown that obesity may have a negative impact on the efficacy of aromatase inhibitors in early breast cancer patients, highlighting the need for further research on optimal endocrine therapies for obese women. However, there is insufficient evidence at present to recommend tailoring adjuvant endocrine therapy with specific AIs or dosing modifications in this patient population.
Article
Oncology
Jankiben R. Patel, Karen M. Gallegos, Rashidra R. Walker, A. Michael Davidson, Ian Davenport, Syreeta L. Tilghman
Summary: The study evaluated the contribution of mammospheres in letrozole-resistant breast cancer, finding that LTLT-Ca tumors expressed CD44(+)/CD24(+) markers, while AC-1 tumors had lower CD44/CD24 expression.
Article
Oncology
Mitch Dowsett, Lucy Kilburn, Mothaffar F. Rimawi, C. Kent Osborne, Katherine Pogue-Geile, Yuan Liu, Samuel A. Jacobs, Melanie Finnigan, Shannon Puhalla, Andrew Dodson, Vera Martins, Maggie Cheang, Sophie Perry, Chris Holcombe, Nick Turner, Claire Swift, Judith M. Bliss, Stephen Johnston
Summary: In postmenopausal women with ER+/HER2(-) primary breast cancer, higher ER and PgR levels were associated with a greater chance of complete cell-cycle arrest, while higher Ki67, c-PARP, and CCNE1 levels were associated with a lower chance. Letrozole decreased CCND1 levels, but palbociclib showed a tendency to increase them. Ki67 recovery within 3-9 days after stopping palbociclib indicates incomplete suppression of proliferation during the off week.
CLINICAL CANCER RESEARCH
(2022)
Article
Nutrition & Dietetics
Jankiben R. Patel, Bipika Banjara, Afia Ohemeng, A. Michael Davidson, Stephen M. Boue, Matthew E. Burow, Syreeta L. Tilghman
Summary: Breast cancer cells that become resistant to letrozole overexpress EGFR, MAPK, and HER2, while also acquiring enhanced motility and EMT-like characteristics, which can be attenuated and reversed by glyceollin treatment. Glyceollin inhibits the proliferation and tumor progression of TNBC and estrogen-independent breast cancer cells, but it may not effectively target AI-resistant metastatic breast cancer in clinical settings. Combination therapy of glyceollin and lapatinib induces apoptosis in hormone-dependent AI-resistant breast cancer cells, and it may also be beneficial for letrozole-resistant breast cancer cells by decreasing proliferation and cell cycle progression-associated proteins. This unique opportunity could lead to the development of novel combination therapies for hormone-refractory breast tumors.
Article
Biochemistry & Molecular Biology
Javier Garcia-Sanchez, Mayra Alejandra Mafla-Espana, Maria Dolores Torregrosa, Omar Cauli
Summary: This study aimed to evaluate the relationship between gonadal hormone concentrations in blood and frailty syndrome, as well as whether these hormone concentrations could predict the progression of frailty syndrome. The results showed that high androstenedione levels and low follicle-stimulating hormone (FSH) levels were significantly associated with the worsening of frailty syndrome. These hormone concentrations could be potential biomarkers to predict the progression of frailty syndrome.
Article
Oncology
Norikazu Masuda, Kenji Tamura, Hiroyuki Yasojima, Akihiko Shimomura, Masataka Sawaki, Min-Jung Lee, Akira Yuno, Jane Trepel, Ryoko Kimura, Yozo Nishimura, Shigehira Saji, Hiroji Iwata
Summary: This study examined the safety, efficacy, and pharmacokinetics of Entinostat monotherapy and combined Entinostat/exemestane in Japanese patients with endocrine therapy-resistant breast cancer. The results showed that both treatments were well tolerated, with some patients achieving stable disease for more than 6 months. Further investigation on the correlation between pharmacokinetics and Ac-K in peripheral blood CD19+ B cells, as well as T-cell activation markers, is warranted.
Article
Oncology
Bora Lim, David A. Potter, Mohamad A. Salkeni, Paula Silverman, Tufia C. Haddad, Frederic Forget, Ahmad Awada, Jean-Luc Canon, Michael Danso, Alain Lortholary, Hugues Bourgeois, Elizabeth Tan-Chiu, Sylvie Vincent, Brittany Bahamon, Kevin J. Galinsky, Chirag Patel, Rachel Neuwirth, E. Jane Leonard, Jennifer R. Diamond
Summary: The study evaluated the efficacy and safety of sapanisertib plus exemestane or fulvestrant in treating advanced/metastatic hormone receptor-positive breast cancer, showing certain clinical benefit for patients. The treatment demonstrated different efficacy in patients previously sensitive or resistant to exemestane.
CLINICAL CANCER RESEARCH
(2021)
Article
Oncology
Ho Tsoi, Johann Lok, Ellen P. S. Man, Cheuk-Nam Cheng, Man-Hong Leung, Chan-Ping You, Sum-Yin Chan, Wing-Lok Chan, Ui-Soon Khoo
Summary: This study revealed that overexpression of a novel splice variant BQ323636.1 is associated with resistance to the non-steroidal aromatase inhibitor anastrozole in ER+ post-menopausal breast cancer. Mechanistic studies showed that BQ overexpression enhances androgen receptor (AR) activity, leading to hyper-activation of AR signaling and increased cell proliferation. Targeting AR can overcome anastrozole resistance in breast cancer with BQ overexpression. Clinical study also demonstrated that high nuclear expression of both BQ and AR is significantly associated with poor survival in non-steroidal aromatase inhibitor-treated ER+ breast cancer patients.
JOURNAL OF PATHOLOGY
(2023)