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Primary central nervous system lymphoma is a rare but aggressive brain malignancy. It is associated with poor prognosis even with the current standard of care. The aim of this study was to evaluate the effect and tolerability of blood-brain barrier disruption treatment combined with high-dose treatment with autologous stem cell transplantation as consolidation on primary central nervous system lymphoma patients. We performed a prospective phase II study for 25 patients with previously untreated primary central nervous system lymphoma. The blood-brain barrier disruption treatment was initiated 3-4 weeks after the MATRix regimen using the previously optimized therapy protocol. Briefly, each chemotherapy cycle included two subsequent intra-arterial blood-brain barrier disruption treatments on days 1 and 2 via either one of the internal carotid arteries or vertebral arteries. Patients received the therapy in 3-week intervals. The treatment was continued for two more courses after achieving a maximal radiological response to the maximum of six courses. The complete treatment response was observed in 88.0% of the patients. At the median follow-up time of 30 months, median progression-free and overall survivals were not reached. The 2-year overall and progression-free survival rates were 67.1% and 70.3%, respectively. Blood-brain barrier disruption treatment is a promising option for primary central nervous system lymphoma with an acceptable toxicity profile.

Background: It is not known whether modifiable lifestyle factors that predict survival after invasive breast cancer differ by subtype., Methods: We analyzed data for 121,435 women diagnosed with breast cancer from 67 studies in the Breast Cancer Association Consortium with 16,890 deaths (8,554 breast cancer specific) over 10 years. Cox regression was used to estimate associations between risk factors and 10-year all-cause mortality and breast cancer-specific mortality overall, by estrogen receptor (ER) status, and by intrinsic-like subtype., Results: There was no evidence of heterogeneous associations between risk factors and mortality by subtype ( P adj > 0.30). The strongest associations were between all-cause mortality and BMI ≥30 versus 18.5-25 kg/m 2 [HR (95% confidence interval (CI), 1.19 (1.06-1.34)]; current versus never smoking [1.37 (1.27-1.47)], high versus low physical activity [0.43 (0.21-0.86)], age ≥30 years versus <20 years at first pregnancy [0.79 (0.72-0.86)]; >0-<5 years versus ≥10 years since last full-term birth [1.31 (1.11-1.55)]; ever versus never use of oral contraceptives [0.91 (0.87-0.96)]; ever versus never use of menopausal hormone therapy, including current estrogen-progestin therapy [0.61 (0.54-0.69)]. Similar associations with breast cancer mortality were weaker; for example, 1.11 (1.02-1.21) for current versus never smoking., Conclusions: We confirm associations between modifiable lifestyle factors and 10-year all-cause mortality. There was no strong evidence that associations differed by ER status or intrinsic-like subtype., Impact: Given the large dataset and lack of evidence that associations between modifiable risk factors and 10-year mortality differed by subtype, these associations could be cautiously used in prognostication models to inform patient-centered care., (©2021 American Association for Cancer Research.)

Toll-like receptor-9 (TLR9) is a DNA receptor widely expressed in cancers. Although synthetic TLR9 ligands induce cancer cell invasion in vitro, the role of TLR9 in cancer pathophysiology is unclear. We discovered that low tumor TLR9 expression is associated with significantly shortened disease-specific survival in patients with triple negative but not with ER+ breast cancers. A likely mechanism of this clinical finding involves differential responses to hypoxia. Our pre-clinical studies indicate that while TLR9 expression is hypoxia-regulated, low TLR9 expression has different effects on triple negative and ER+ breast cancer invasion in hypoxia. Hypoxia-induced invasion is augmented by TLR9 siRNA in triple negative, but not in ER+ breast cancer cells. This is possibly due to differential TLR9-regulated TIMP-3 expression, which remains detectable in ER+ cells but disappears from triple-negative TLR9 siRNA cells in hypoxia. Our results demonstrate a novel role for this innate immunity receptor in cancer biology and suggest that TLR9 expression may be a novel marker for triple-negative breast cancer patients who are at a high risk of relapse. Furthermore, these results suggest that interventions or events, which induce hypoxia or down-regulate TLR9 expression in triple-negative breast cancer cells may actually induce their spread.

Hyaluronan, a major macropolysaccharide in the extracellular matrix of connective tissues, is intimately involved in the biology of cancer. Hyaluronan accumulates into the stroma of various human tumors and modulates intracellular signaling pathways, cell proliferation, motility and invasive properties of malignant cells. Experimental and clinicopathological evidence highlights the importance of hyaluronan in tumor growth and metastasis. A high stromal hyaluronan content is associated with poorly differentiated tumors and aggressive clinical behavior in human adenocarcinomas. Instead, the squamous cell carcinomas and malignant melanomas tend to have a reduced hyaluronan content. In addition to the stroma-cancer cell interaction, hyaluronan can influence stromal cell recruitment, tumor angiogenesis and epithelial-mesenchymal transition. Hyaluronan receptors, hyaluronan synthases and hyaluronan degrading enzymes, hyaluronidases, are involved in the modulation of cancer progression, depending on the tumor type. Furthermore, intracellular signaling and angiogenesis are affected by the degradation products of hyaluronan. Hyaluronan has also therapeutic implications since it is involved in multidrug resistance., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Objectives: Adjuvant trastuzumab is widely used in HER2-positive (HER2+) early breast cancer, and despite its cost-effectiveness, it causes substantial costs for health care. The purpose of the study was to develop a tool for estimating the budget impact of new cancer treatments. With this tool, we were able to estimate the budget impact of adjuvant trastuzumab, as well as the probability of staying within a given budget constraint., Methods: The created model-based evaluation tool was used to explore the budget impact of trastuzumab in early breast cancer in a single Finnish hospital district with 250,000 inhabitants. The used model took into account the number of patients, HER2+ prevalence, length and cost of treatment, and the effectiveness of the therapy. Probabilistic sensitivity analysis and alternative case scenarios were performed to ensure the robustness of the results., Results: Introduction of adjuvant trastuzumab caused substantial costs for a relatively small hospital district. In base-case analysis the 4-year net budget impact was 1.3 million euro. The trastuzumab acquisition costs were partially offset by the reduction in costs associated with the treatment of cancer recurrence and metastatic disease., Conclusions: Budget impact analyses provide important information about the overall economic impact of new treatments, and thus offer complementary information to cost-effectiveness analyses. Inclusion of treatment outcomes and probabilistic sensitivity analysis provides more realistic estimates of the net budget impact. The length of trastuzumab treatment has a strong effect on the budget impact.

Aims and Background: Hair loss is one of the most unpleasant side effects associated with chemotherapy treatments. It causes emotional disturbances and constantly reminds the patient of the disease. This study analyzed the effectiveness of scalp cooling caps in preventing alopecia among 64 patients., Methods: The patients were given one of the following chemotherapeutic treatments: doxorubicin 60 mg/m2, docetaxel 80 mg/m2, FEC (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2) or the combination of three cycles of docetaxel (80 mg/m2) followed by three cycles of FEC (5-fluorouracil 600 mg/m2, epirubicin 60 mg/m2, cyclophosphamide 600 mg/m2). All the chemotherapy treatments were given in a three-weekly schedule. Patients with early stage disease were given six adjuvant chemotherapy cycles, while patients with metastatic disease were given nine chemotherapy cycles. The patients were provided with detailed instructions on how to treat the hair at home for one to three days after the chemotherapy treatment. Hair loss was evaluated after the third, sixth and final treatments., Results: In the final results, major hair loss was avoided in all patients given doxorubicin treatment, in 83.3% of patients given docetaxel treatment, in 76.5% of patients given FEC treatment, and in 78% of patients given docetaxel followed by FEC. In the final evaluation, 87.5% of the patients considered the avoidance of hair loss to be important. Only 20.3% of the patients needed to use a wig., Conclusions: This study shows that all the patient groups studied gained some benefit by using scalp cooling caps.

Hyaluronan (HA) is one of the extracellular-matrix components involved in wound healing, tumour growth and metastasis. Due to the limited data on HA expression in benign and malignant breast lesions, we analyzed its presence in these lesions by using the biotinylated-hyaluronan-binding region and the link-protein complex (bHABC) of cartilage proteoglycan as a specific probe. In all benign breast lesions, the expression of HA was restricted to the stromal connective tissue, the ductal epithelial cells being completely devoid of HA. In malignant breast tumours, the intensity of stromal HA staining was significantly stronger than in benign lesions. In addition, HA was detected on cell membranes or in cytoplasms of adenocarcinoma cells, in some cases of ductal carcinoma in situ and in 31% of malignant tumours. The staining pattern was mostly similar in all breast-cancer types studied, i.e., ductal, lobular, tubular, mucinous and medullary. In ductal breast cancer, intense HA expression in stroma and carcinoma cells correlated statistically significantly to poor differentiation of carcinoma, suggesting that altered HA expression may affect the mechanisms of breast-cancer progression.

A series of breast cancer biopsies from 204 women were analysed immunohistochemically for the expression of transforming growth factor alpha (TGF-alpha). Expression of TGF-alpha was intense in 119 cases (58%), weak in 63 (31%), and totally absent in 22 (11%) of the cases. No correlation was observed between the expression of TGF-alpha and tumour size, metastasis at diagnosis, histological type and grade, ER and PR status, DNA index, S-phase fraction or the expression of TGF-beta1 or beta2. However, the expression of TGF-alpha was significantly related to axillary lymph node metastasis and to low survival probability during the follow-up. These data support the earlier observations on the in vitro studies, suggesting that TGF-alpha most probably exerts an in vivo growth stimulation of female breast cancer cells.