Papers by Elżbieta Senkus
Nature Reviews Clinical Oncology, 2015
International journal of clinical and experimental pathology, 2014
The biology and pathomechanism of bilateral breast cancers is not fully understood. We compared t... more The biology and pathomechanism of bilateral breast cancers is not fully understood. We compared the morphological and immunohistochemical characteristics of primary tumors in patients with synchronous bilateral breast cancers and metachronous bilateral breast cancers, with special focus on intrinsic tumor phenotype. Tumor morphology and expression of 8 immunohistochemical markers were assessed in tissue microarrays containing primary breast tumor cores from 113 metachronous bilateral breast cancers and 61 synchronous bilateral breast cancers. Analyzed markers included hormone receptors (estrogen receptor, progesterone receptor), HER2, Ki67, cytokeratin 5/6, E-cadherin, vimentin and epidermal growth factor receptor. Cutoff levels are provided in the table. Metachronous bilateral breast cancers tumors had lower estrogen receptor expression (p=0.047) and higher expression of cytokeratin 5/6 (p=0.017) and of vimentin (p=0.008); in multivariate analysis only vimentin retained the signifi...
Pathology international, 2014
Patients with bilateral breast cancer (BBC) and breast-ovarian cancer syndrome (BOCS) constitute ... more Patients with bilateral breast cancer (BBC) and breast-ovarian cancer syndrome (BOCS) constitute populations potentially enriched for molecular defects involved in the pathomechanisms of these malignancies. The aim of our study was to compare tumor morphology and expression of estrogen and progesterone receptor, HER2, Ki67, cytokeratin 5/6, E-cadherin, vimentin and epidermal growth factor receptor in tissue microarrays from 199 tumors from BBC or BOCS patients and 199 age-matched solitary tumors. Compared to controls, BBC and BOCS considered jointly had lower incidence of DCIS, lower expression of PgR and HER2, and higher expression of Ki67 and vimentin. BOCS tumors were of higher grade, had lower expression of ER and PgR and higher expression of Ki67, CK5/6, vimentin and EGFR. BBC had less DCIS component, lower HER2 expression and higher Ki67 expression. Metachronous BBC (mBBC) had lower expression of ER, PgR and HER2, and higher expression of Ki67 and vimentin. Synchronous BBC (sB...
Reports of Practical Oncology & Radiotherapy, 2001
Nature reviews. Clinical oncology, 2015
Locally advanced breast cancer (LABC) constitutes a heterogeneous entity that includes advanced-s... more Locally advanced breast cancer (LABC) constitutes a heterogeneous entity that includes advanced-stage primary tumours, cancers with extensive nodal involvement and inflammatory breast carcinomas. Although the definition of LABC can be broadened to include some large operable breast tumours, we use this term to strictly refer to inoperable cancers that are included in the above-mentioned categories. The prognosis of such tumours is often unfavourable; despite aggressive treatment, many patients eventually develop distant metastases and die from the disease. Advances in systemic therapy, including radiation treatment, surgical techniques and the development of new targeted agents have significantly improved clinical outcomes for patients with this disease. Notwithstanding these advances, LABC remains an important clinical problem, particularly in developing countries and those without widely adapted breast cancer awareness programmes. The optimal management of LABC requires a multidis...
Nature Reviews Clinical Oncology, 2015
In 2014, no major breakthroughs were made in understanding the biology of breast cancer or its ma... more In 2014, no major breakthroughs were made in understanding the biology of breast cancer or its management; few novel practice-changing studies were presented or published. Nevertheless, important negative results from studies that challenge some of the current concepts, particularly in drug development, underline 2014 as a year of ‘failed surrogates and precocious expectations’.
Psycho-Oncology, 2013
Infertility due to anticancer treatments is a major source of distress for young patients with ca... more Infertility due to anticancer treatments is a major source of distress for young patients with cancer. A survey was performed among breast cancer patients younger than 35 years, to evaluate the acceptance of chemotherapy in the context of infertility risk. After obtaining written informed consent, we asked 400 premenopausal, early stage breast cancer patients aged ≤35 years to complete a short, previously pilot-tested questionnaire. Three hundred and eighty-nine patients were evaluable. The association between the explanatory variables and the outcome variables was assessed using logistic regression. Two hundred and twenty-eight (59%) participants wanted to have (more) children in the future, whereas 158 (41%) did not. Fifty-seven (36%) of the latter did not want additional children because of fear of cancer recurrence. Thirty-two women (8%) stated they would not accept chemotherapy should it reduce their fertility. This was dependent upon already having children, the wish to have (further) children, geographical area, disease stage, and already planned chemotherapy. One hundred and seventy-one women who would agree to chemotherapy (48%) would accept a risk of infertility of 76-100%. This acceptance was dependent on already having children and the wish to have (more) children. Of the 355 participants (91%) accepting chemotherapy, 48 would accept it only for ≥20% gain in cure. For the majority of young patients with breast cancer, cure remains their first priority; for this, they are willing to accept a considerable decrease in future fertility, and only less than 10% will forego chances of cure to preserve fertility.
The Breast, 2013
Rationale: Bilateral breast cancers (BBC) and breast cancers coexisting with ovarian cancer (BOCS... more Rationale: Bilateral breast cancers (BBC) and breast cancers coexisting with ovarian cancer (BOCS) are associated with genetic predisposition more frequently than sporadic cases. We compared the phenotypes of these tumors to better understand their pathomechanisms and aid the guiding of their clinical management. Materials and methods: Tumor morphology and expression of ER, PgR, HER2, Ki67, CK5/6, E-cadherin, vimentin and EGFR were assessed in a tissue microarray containing cores from 174 BBC, 23 BOCS and 2 BBC þ BOCS. Results: BOCS tumors were characterized by higher incidence of EGFR expression, HER2 negativity and lower incidence of intraductal component. HER2-positive phenotypes were marginally more frequent in the BBC group and triple negative tumors e in BOCS. Conclusion: Breast cancers from BOCS patients are characterized by more aggressive phenotype, most probably related to their more frequent association with BRCA1 mutation.
Strahlentherapie und Onkologie, 1997
Aim: Although the relationship between the dose delivered to adjacent organs (urinary bladder and... more Aim: Although the relationship between the dose delivered to adjacent organs (urinary bladder and rectum) and the frequency and severity of treatment complications has been reported in many series, the factors influencing pelvic dose distribution ate not welt defined. The aim of the study was to assess retrospectively the influence of the size of cervical cancer brachytherapy applicators (ovoids and uterine tandems) on pelvic dose distribution and the impact of various therapy-dependent factors on patient anatomy and on dose distribution in particular applications. Patients and Method: The subject of this study were 356 cervical cancer patients treated with Selectron LDR as a part of their radical radiotherapy. Analysed factors included preceding external beam radiotherapy (EBRT) or brachytherapy applications, use of general anaesthesia for application and the system of pellet loading. Results: Significant correlation was found between the size of applicators and doses to bladder, rectum and points B: larger vaginal applicators produced lower dose in bladder and rectum and higher dose in point B (all p < 0.0001), longer uterine tandems produced lower dose in rectum and higher dose in point B (both p < 0.0001). Significant decrease in the frequency of use of large applicators (ovoids: p < 0.0001, tandems: p = 0.055) and worsening of dose distribution, i.e. higher doses to critical organs (respectively: bladder p = 0.0012, rectum p = 0.02) and lower point B dose (p = 0,0001) were observed at consecutive brachytherapy applications. Similar situation occurred in patients, who received EBRT prior to brachytherapy (ovoids: p < 0.001, tandem: p = 0.04, bladder dose: p=0.009, rectal dose: p=0.073, point B dose: p=0.059). Vaginal applicators were larger (p = 0.026) and the dose distribution was better (bladder: p = 0.023, rectum: p = 0.002, point B: p = 0.0001) in patients who had their insertions performed under general anaesthesia. The comparison of 2 consecutively used systems of pellet loading revealed more favourable dose distribution: lower dose for bladder (p = 0.014) and higher dose for point B (p < 0.0001) for the system, which utilised more sources in ovoids and in the distal part of the uterine tandem, in spite of more frequent use of smaller applicators in this group of patients. In multivariate analysis ovoid size was related to preceding external beam radiotherapy (p = 0.025). Uterine tandem length was dependent on the number of preceding intracavitary applications (p < 0.001) and preceding external beam radiotherapy (p = 0.007). Bladder dose was related to preceding brachytherapy (p = 0.011) and the pattern of pellet loading (p =0.031). Rectal dose was dependent only on the use of general anaesthesia during application (p = 0.001) and point B dose was dependent on the pattern of pellet loading (p < 0.001) and marginally -on the use of preceding external beato radiotherapy (p = 0.06), Conelusions: The results of this study allow for identification of treatment-related factors determining pelvic dose distribution in cervical cancer brachytherapy and may potentially enable optimisation of this distribution in particular clinical situation.
Oncology Reports, 2008
Sixty-four Polish families with a history of breast and/or ovarian cancer were screened for mutat... more Sixty-four Polish families with a history of breast and/or ovarian cancer were screened for mutations in the BRCA1/2 genes using a combination of denaturing high performance liquid chromatography (DHPLC) and sequencing. Two thirds (43/64; 67%) of the families were found to carry deleterious mutations, of which the most frequent were BRCA1 5382insC (n=22/43; 51%) and Cys61Gly (n=9/43; 20%). Two other recurrent mutations were BRCA1 185delAG (n=3) and 3819del5 (n=4), together accounting for 16% of the 43 mutation-positive cases. We also found three novel mutations (BRCA1 2991del5, BRCA2 6238ins2del21 and 8876delC) which combined with findings from our earlier study of 60 Northern Polish families. Moreover, screening of 43 BRCA1/2 negative families for the presence of large rearrangements by multiplex ligation-dependent probe amplification (MLPA) resulted in the finding of two additional BRCA1 mutations: a deletion of exons 1A, 1B and 2, and a deletion of exons 17-19, both present in single families. We conclude that the Polish population has a diverse mutation spectrum influenced by strong founder effects. However, families with strong breast/ovarian cancer history who are negative for these common mutations should be offered a complete BRCA gene screening, including MLPA analysis.
International Journal of Radiation Oncology*Biology*Physics, 1997
The aim of this study was to assess retrospectively the influence of the size of cervical cancer ... more The aim of this study was to assess retrospectively the influence of the size of cervical cancer brachytherapy applicators (ovoids and uterine tandems) on pelvic dose distribution and to analyze the impact of various patient- and disease-related factors on applicators&#39; geometry and on dose distribution in particular applications. The subject of this study were 356 cervical cancer patients treated with Selectron LDR as a part of their radical radiotherapy. Analyzed factors included patient age, weight, number of vaginal deliveries, and disease stage. The use of larger vaginal applicators resulted in lower bladder and rectum doses and in higher point B doses (all p &lt; 0.0001); longer uterine tandems produced lower rectum doses and higher point B doses (both p &lt; 0.0001). Increasing patient age and disease stage resulted in a decreased frequency of use of large ovoids (both p &lt; 0.0001) and of long tandems (age: p = 0.0069, stage: p = 0.004). As a result, higher doses to bladder (age: p &lt; 0.0001, stage: p = 0.017) and rectum (age: p = 0.037, stage: p = 0.011) were observed. Increasing age also resulted in lower point B doses (p &lt; 0.0001). Increasing patient weight correlated with less frequent use of long tandems (p = 0.0015) and with higher bladder doses (p = 0.04). Higher number of vaginal deliveries was related to the increase in the use of long tandems (p = 0.002); in patients who had had at least one vaginal delivery, point B doses were significantly higher (p = 0.0059). In multivariate analysis ovoid size and uterine tandem length were dependent on patient age (respectively: p &lt; 0.001 and p = 0.001), disease stage (respectively: p = 0.003 and p = 0.008) and on the number of vaginal deliveries (respectively: p = 0.07 and p = 0.008). Doses to critical organs and to points B were dependent on patient age (respectively: p &lt; 0.001, p = 0.011, and p &lt; 0.001) and on disease stage (respectively: p &lt; 0.001, p = 0.004, and p = 0.048). The results of this study allow for identification of some patient- and disease-related factors influencing pelvic dose distribution in cervical cancer brachytherapy. This potentially may enable optimization of the dose distribution in particular clinical situations.
International Journal of Radiation Oncology*Biology*Physics, 2012
Background: Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer. The aim of this retro... more Background: Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer. The aim of this retrospective study was to assess prognostic factors and patterns of failure, as well as the role of radiation therapy (RT), in ACC. Methods: Between January 1980 and December 2007, 61 women with breast ACC were treated at participating centers of the Rare Cancer Network. Surgery consisted of lumpectomy in 41 patients and mastectomy in 20 patients. There were 51(84%) stage pN0 and 10 stage cN0 (16%) patients. Postoperative RT was administered to 40 patients (35 after lumpectomy, 5 after mastectomy). Results: With a median follow-up of 79 months (range, 6-285), 5-year overall and disease-free survival rates were 94% (95% confidence interval [CI], 88%-100%) and 82% (95% CI, 71%-93%), respectively. The 5-year locoregional control (LRC) rate was 95% (95% CI, 89%-100%). Axillary lymph node dissection or sentinel node biopsy was performed in 84% of cases. All patients had stage pN0 disease. In univariate analysis, survival was not influenced by the type of surgery or the use of postoperative RT. The 5-year LRC rate was 100% in the mastectomy group versus 93% (95% CI, 83%-100%) in the breast-conserving surgery group, respectively (p = 0.16). For the breast-conserving surgery group, the use of RT significantly correlated with LRC (p = 0.03); the 5-year LRC rates were 95% (95% CI, 86%-100%) for the RT group versus 83% (95% CI, 54%-100%) for the group receiving no RT. No local failures occurred in patients with positive margins, all of whom received postoperative RT. Conclusion: Breast-conserving surgery is the treatment of choice for patients with ACC breast cancer. Axillary lymph node dissection or sentinel node biopsy might not be recommended. Postoperative RT should be proposed in the case of breast-conserving surgery. Ó 2012 Elsevier Inc.
Cancer Treatment Reviews, 2011
Many methods of systemic anticancer treatment have detrimental effects on the cardiovascular syst... more Many methods of systemic anticancer treatment have detrimental effects on the cardiovascular system, thus limiting the possibility of further therapy, worsening patients' quality of life and increasing mortality. The best recognized and most clinically relevant is the cardiotoxicity of anthracyclines. Other cytotoxic drugs associated with significant risk of cardiovascular complications include alkylating agents, 5-fluorouracil and paclitaxel. Cardiovascular adverse effects are also associated with the use of targeted therapies, such as trastuzumab, bevacizumab and tyrosine kinase inhibitors, and some of the drugs used in the treatment of hematological malignancies, such as all-trans-retinoic acid and arsenic trioxide.
Acta Obstetricia et Gynecologica Scandinavica, 2000
Background. Patients after treatment for cervical cancer have increased risk of developing second... more Background. Patients after treatment for cervical cancer have increased risk of developing second squamous cell malignancy of the lower genital tract. Material and methods. A retrospective study of 46 patients with second lower genital tract epidermoid cancers following previous treatment for invasive cervical carcinoma. Results. Patient age at diagnosis of cervical cancer was 27 to 68 years (median 44 years) and at diagnosis of the second malignancy -43 to 72 years (median 63 years). There were four cases (9%) of synchronous cancers. Time span between metachronous malignancies ranged from 66 to 406 months (median 206 months). In 32 cases (70%) second lesion was located in the vagina and in 14 (30%) -in the vulva. Out of 35 previously irradiated patients, in 24 (69%) second tumor was located within the high dose volume and in 11 (31%) -outside it. Treatment of second cancer consisted of surgery in 12 patients (26%), radiotherapy -in 23 (50%), combined surgery and radiotherapy -in five (11%), chemotherapy -in four (9%) and surgery plus chemotherapy -in one case. Median survival was 52 months and five-year survival from the diagnosis of second malignancy -47.5%. No prognostic factors for survival were identified. Conclusion. Treatment outcome in patients with second lower genital tract carcinoma is unsatisfactory due to poor feasibility of another definite treatment after previous radical surgery and/or radiotherapy.
Cancer Treatment Reviews, 2014
Treatment of metastatic breast cancer has substantially changed in the last decades. Availability... more Treatment of metastatic breast cancer has substantially changed in the last decades. Availability of new cytotoxics and targeted therapies as well as changes in treatment philosophy and strategy have all contributed to a significant improvement in both survival and patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; quality of life. The multidisciplinary approach, personalised treatments based on tumour characteristics, patient&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s and disease history, as well as re-definition of treatment goals, aiming at the lowest possible impact on patients&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39; life by replacing aggressive multidrug chemotherapy with single-agent cytotoxic treatment or endocrine±targeted therapies, have all been the bases of the new treatment paradigm. More recently the development of the international advanced breast cancer (ABC) consensus guidelines have further contributed to this improvement. This review will focus on the major achievements and challenges in the different tumour subtypes and sites, with a focus on future research topics and trends.
JNCI Journal of the National Cancer Institute, 2009
Compared with treatment options for early-stage breast cancer, few data exist regarding the optim... more Compared with treatment options for early-stage breast cancer, few data exist regarding the optimal use of chemotherapy for metastatic breast cancer (MBC). The choice of using a combination of cytotoxic chemotherapies vs sequential single agents is controversial. At the 6th European Breast Cancer Conference, the European School of Oncology Metastatic Breast Cancer Task Force convened an open debate on the relative benefits of combination vs sequential therapy. Based on the available data, the Task Force recommends sequential monotherapy as the preferred choice in advanced disease, in the absence of rapid clinical progression, life-threatening visceral metastases, or the need for rapid symptom and/or disease control. Patient-and diseaserelated factors should be used to choose between combination and sequential single-agent chemotherapy for MBC. Additional research is needed to determine the impact of therapy on patient-rated quality of life and to identify predictive factors that can be used to guide therapy. JNCI | Commentary 1175 * A = doxorubicin; A + Doc* = doxorubicin 50 mg/m 2 and docetaxel 75 mg/m 2 ; A + Doc † = doxorubicin 60 mg/m 2 and docetaxel 60 mg/m 2 ; Doc = docetaxel; E = epirubicin; G = gemcitabine; MF = methotrexate-5-fluorouracil; NR = not reported; Pac = paclitaxel; X = capecitabine. † Infection including febrile neutropenia. by guest on June 1, 2015
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Papers by Elżbieta Senkus