Tartós SARS-CoV-2-PCR-pozitivitáshoz társuló, lokoregionálisan előrehaladott emlődaganat komplex onkológiai kezelése

Összefoglaló. A COVID–19 mortalitását a súlyos társbetegségek, közöttük bizonyos daganatos betegségek is növelik. Immunszuppresszív hatásuk miatt felmerülhet a citotoxikus kezelések rizikónövelő hatása is. Ugyanakkor az onkológiai terápia megszakítása vagy halasztása, különösen az agresszívebb, kiterjedtebb és fiatalkorban jelentkező daganatok esetében ronthatja a kórjóslatot. Egy 39 éves nőbeteg esetét ismertetjük. A járvány során késlekedve felismert, lokoregionálisan kiterjedt emlődaganat miatt primer szisztémás kemoterápiában részesült. A kezelés 5. ciklusa során enyhe légúti tünetek kapcsán, az onkológiai ambulancián SARS-CoV-2-fertőzése igazolódott. Kemoterápiás kezelését felfüggesztettük. A diagnózistól számított 3. napon tünetmentessé vált, ám SARS-CoV-2-PCR-pozitivitása még a 43. napon is fennállt. A 19. napon hormongátló kezelést indítottunk. Az 51. napon mastectomia és axillaris block dissectio történt. A 82. napon a megszakított kemoterápiát a hormongátló kezelés leállítását követően G-CSF-profilaxis mellett újraindítottuk. A kezelés során fertőzéses szövődményt nem észleltünk. Kemoterápia és műtét SARS-CoV-2-fertőzött, tünetmentes daganatos betegnél szövődménymentesen végezhető elhúzódó virológiai pozitivitás esetén, felszabadító vizsgálat nélkül is. A daganatos betegek koronavírus-fertőzése esetén az onkológiai protokolltól történő eltérés egyénre szabott optimalizálásával és a multidiszciplináris team szorosabb együttműködésével az infektológiai és az onkológiai kockázat együttes alacsonyan tartása is megvalósítható. Orv Hetil. 2021; 162(16): 611–614. Summary. Mortality of COVID-19 is increased when certain co-morbidities, among others advanced malignancies are present. Deleterious effect of cytotoxic therapy, related to its immunosuppressive effect, may also be hypothesised. However, postponing or cancelling oncologic treatment, especially in younger patients with advanced and more aggressive tumors may worsen the prognosis. The case of a 39-year-old female patient is presented, who was diagnosed with loco-regionally advanced breast cancer during the pandemic. Primary systemic chemotherapy was started. The patient presented with acute respiratory tract symptoms during the fifth cycle and subsequently SARS-CoV-2 infection was diagnosed. Chemotherapy was cancelled. Symptoms resolved in three days after diagnosis. SARS-CoV-2 PCR remained positive up to day 43. Antihormonal therapy was introduced on day 19 and she underwent mastectomy with axillary lymph node dissection on day 51. Chemotherapy was reset postoperatively on day 82 with prophylactic G-CSF protection. No adverse event was observed throughout the treatment. Cytotoxic chemotherapy and surgery can be successfully delivered in breast cancer patients with prolonged asymptomatic SARS-CoV-2 PCR positivity, even without negative swab result. Individual optimisation of the therapy may require deviations from standard protocols. Closer multidisciplinary cooperation may contribute to the minimisation of both oncologic and infectious risks. Orv Hetil. 2021; 162(16): 611–614.

Real-world clinical outcomes study of sequential novel antihormonal therapy (NAH) or radium-223 (Ra-223) treatment of metastatic castration-resistant prostate cancer (mCRPC) that progressed after first-line NAH.

48 Background: We assessed real-life clinical outcomes in patients with mCRPC treated in the USA who received sequential first-line (1L)/second-line (2L) NAH (abiraterone/enzalutamide or enzalutamide/abiraterone) or switched to a different mechanism of action (alpha-emitter Ra-223) after progression on 1L NAH. Methods: This was a retrospective study (PHENIX, NCT03896984) of the Flatiron electronic health record database in patients with mCRPC that progressed on 1L NAH and started 2L monotherapy with Ra-223 (n=120) or NAH (n=226) between Jan 2013 and Dec 2018. Patient characteristics, overall survival (OS) from 2L start, and symptomatic skeletal events (SSEs) were analyzed descriptively. Results: The two cohorts were generally similar at 2L start, including similar rates of bone-health agent (BHA) use, but the Ra-223 cohort had a higher incidence of bone-only metastases, shorter duration of 1L NAH, and higher rate of prior SSEs than the 2L NAH cohort (Table). Median treatment duration was 5.6 mo (median 4.5 doses) for Ra-223 and 4.7 mo for 2L NAH. Median OS from 2L start was 10.8 mo for Ra-223 and 11.2 mo for 2L NAH, with 49% and 39%, respectively, receiving subsequent therapy. Among those who received subsequent therapy, the proportion who received subsequent taxane was lower in the Ra-223 cohort (47%) than in the 2L NAH cohort (76%). SSEs were observed after 2L start in 32 patients (27%) on Ra-223 and 49 (22%) on 2L NAH. Conclusions: OS from start of 2L mCRPC treatment was similar for patients who received Ra-223 or alternative NAH in 2L. Slightly more patients received subsequent therapy in the Ra-223 cohort than in the 2L NAH cohort. Patients who received subsequent therapy were more likely to receive chemotherapy in the 2L NAH cohort, which is unsurprising as 2L NAH after 1L NAH is not highly active. Although the prior SSE rate before 2L start was higher in the Ra-223 cohort than in the 2L NAH cohort, and the two cohorts had similar rates of BHA use at 2L start, the rate of SSEs after 2L start was similar in both cohorts. Clinical trial information: NCT03896984. [Table: see text]

KEYNOTE-365 cohort B updated results: Pembrolizumab (pembro) plus docetaxel and prednisone in abiraterone (abi) or enzalutamide (enza)-pretreated patients (pts) with metastatic castrate-resistant prostate cancer (mCRPC).

103 Background: KEYNOTE-365 (NCT02861573) is a phase 1b/2 study to evaluate pembro in combination with other agents in mCRPC. Here we report updated results from cohort B (pembro + docetaxel and prednisone). Methods: Cohort B enrolled pts who failed or were intolerant to ≥4 wk of abi or enza in the prechemotherapy mCRPC state and whose disease progressed within 6 mo of screening as determined by PSA progression or radiologic bone/soft tissue progression. Pts received pembro 200 mg IV + docetaxel 75 mg/m2 IV Q3W and prednisone 5 mg orally twice daily. Primary end points were safety, PSA response rate (confirmed PSA decrease >50%), and ORR per blinded independent central review (BICR). Results: Of 104 treated pts, 72 discontinued, primarily due to progression (55%). Median age was 68 y (range 50-86), 24% were PD-L1+, 25% had visceral disease, and 50% had measurable disease. Median follow-up was 13 mo for all pts (n=104) and 19 mo for pts who had ≥27 wk of follow up (n=72). See table for efficacy outcomes. Treatment-related AEs occurred in 100 pts (96%); most frequent (≥30%) were alopecia, diarrhea, and fatigue (39% each). Grade 3-5 treatment-related AEs occurred in 42 pts (40%). Five pts died of AEs; 2 deaths were from treatment-related AEs (pneumonitis). Conclusions: With additional follow-up, pembro + docetaxel and prednisone continued to show activity in pts with mCRPC who failed previous antihormonal therapy. Safety of the combination was consistent with the known profiles of the individual agents and will be further evaluated in a phase 3 study (KEYNOTE-921). Clinical trial information: NCT02861573. [Table: see text]

Estrogen receptor α regulates the expression of syndecan-1 in human breast carcinoma cells

Breast cancer (BC) is the primary cause of cancer-related mortality among women. Patients who express the estrogen receptor (ER), which mediates the tumorigenic effects of estrogens, respond to antihormonal therapy. Loss of ER expression or acquired resistance to E2 is associated with aggressive malignant phenotypes, which lead to relapse. These BC subtypes overexpress syndecan-1 (SDC1), a transmembrane heparan sulfate proteoglycan that mediates angiogenesis as well as the proliferation and invasiveness of cancer cells. We showed here that the activation of ER-alpha (ERα) by estrogens induces downregulation of SDC1 expression in ER(+) MCF7 cells but not in T47D cells. Loss of ERα expression, induced by RNA interference or a selective ER downregulator, led to subsequent SDC1 overexpression. E2-dependent downregulation of SDC1 expression required de novo protein synthesis and was antagonized by treatment with BAY 11-7085, an irreversible inhibitor of IκBα phosphorylation, which inhibits the activation of NFκB. Downregulation of SDC1 expression required ERα and activation of IKK, but was independent to downstream transcriptional regulators of NFκB. BAY 11-7085 prevented E2-mediated phosphorylation of ERα on Ser118, increasing its proteasomal degradation, suggesting that IKK stabilized E2-activated ERα, leading to subsequent downregulation of SDC1 expression. Our results showed that sustained ER signaling inhibits SDC1 expression. Such antagonism elucidates the inverse correlation between SDC1 and ER expression in ER(+) BC as well as the overexpression of SDC1 in hormone receptor-negative BC subtypes with the most aggressive phenotypes. These results identify SDC1 as an attractive therapeutic target for BC as well as for other endocrine-associated cancers.

Aromatase Inhibitor-Associated Tendinopathy and Muscle Tendon Rupture: Report of Three Cases of This Exceedingly Rare Adverse Event

Aromatase inhibitors (AIs) are a commonly used antihormonal therapy in the treatment of breast cancer in postmenopausal women, specifically in the treatment of hormone receptor-positive breast cancer. AI-associated tendinopathy and muscle tendon rupture is exceedingly rare. Until now, only one case with AI-associated severe tendinopathy has been reported in the medical literature, and there are no recorded cases of AI-associated muscle tendon rapture. We report three cases of postmenopausal women with hormone receptor-positive breast cancer, who experienced tendinopathy or muscle tendon rupture under antihormonal treatment with letrozole. All of the three women were in the adjuvant setting, and the treatment of tendinopathy or tendon rupture consisted of AI discontinuation, initiation of corticosteroids, or surgical treatment. Diagnosis was made via MRI. Furthermore, in our cases, there were no signs of underlying systemic disease, there was no abnormal physical activity preceding the complaints, and there was no use of other drugs beside letrozole. AIs are one of the most commonly used drugs in antihormonal therapy for hormone receptor-positive breast cancer. In every case of a female patient with hormone receptor-positive breast cancer under treatment with AIs and arthralgia, an MRI should be performed in order to exclude the presence of tendinopathy or muscle tendon rupture.

BREAST CANCER IN MEN IN THE REPUBLIC OF BASHKORTOSTAN

Breast cancer in men is 100 times less common than in women. The principles of treatment of breast cancer in men are still based on knowledge obtained during the treatment of women with a similar pathology. The article reviews 67 cases of all breast cancer stages in men. The majority (50.7%) of all patients who initiated therapy had stage III-IV tumors. In most cases, the patients had an infiltrating ductal carcinoma (52.2%). The combination and complex treatment methods accounted for 53.6% of all cases. The radical mastectomy (89.6%) was the most frequent method of operative intervention. 29 patients (43.3%) received preoperative chemotherapy. 36 patients received adjuvant treatment. The adjuvant treatment comprised chemotherapy (29 patients), and subsequently was supplemented with antihormonal therapy in patients with receptor-positive tumors. The anthracycline-containing chemotherapy was the most prevalent among treatment regimens (72.4%). In 7 patients with a locally diffused process, the treatment was supplemented with radiotherapy. 72.2% of patients had a clinically significant estrogen receptor (RE) expression in the tumor and 61% of patients had a progesterone receptor (RP) expression. 85.0% of patients with stages I-IIA breast cancers showed the relatively high 5-year survival rates, and 67.5% of patients with stage IIB cancers showed 5-year survival. The survival rates for stages III and IV cancer were 18.1% and 16.6%, respectively.