Publications by authors named "D B Geffen"

83 Publications

Neoadjuvant therapy with doxorubicin-cyclophosphamide followed by weekly paclitaxel in early breast cancer: a retrospective analysis of 200 consecutive patients treated in a single center with a median follow-up of 9.5 years.

Breast Cancer Res Treat 2022 Jun 22;193(3):597-612. Epub 2022 Apr 22.

Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Purpose: We analyzed outcomes of doxorubicin-cyclophosphamide (AC) followed by weekly paclitaxel as neoadjuvant chemotherapy (NAC) for breast cancer (BC), in an everyday practice with long-term follow-up of patients.

Methods: All patients (n = 200) who received the AC-paclitaxel combination as NAC for BC at the Soroka University Medical Center from 2003 to 2012 were included in this retrospective cohort study. AC was administered on an every 3-week schedule (standard dose) until May, 2007 (n = 99); and subsequently every 2-week dose dense (dd) (n = 101). Clinical pathologic features, treatment course, and outcome information were recorded. Complete pathologic response (pCR) was analyzed according to BC subtype, dose regimen, and stage.

Results: Median age was 49 years; 55.5% and 44.5% of patients were clinically stage 2 and 3, respectively. Standard dose patients had more T3 tumors. Subtypes were human epidermal growth factor receptor-2 (HER2)-positive 32.5% (of whom 82% received trastuzumab), hormone receptor-positive/HER2-negative 53%, and triple negative 14.5%. Breast-conserving surgery (BCS) was performed in 48.5% of patients; only 9.5% were deemed suitable for BCS prior to NAC. Toxicity was acceptable. The overall pCR rate was 26.0% and was significantly higher in the dd group and HER2-positive patients. With a median follow-up of 9.51 years median event-free survival (EFS) and overall survival (OS) are 10.85 years and 12.61 years, respectively. Patients achieving pCR had significantly longer EFS and OS.

Conclusion: NAC for BC with AC-paclitaxel can be safely administered in the "real-world' setting with high efficacy. Current efforts are aimed at increasing rates of pCR and identifying patients who may benefit from additional therapy or conversely, de-escalated treatment.
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http://dx.doi.org/10.1007/s10549-022-06598-0DOI Listing
June 2022

Bone mineral density in women newly diagnosed with breast cancer: a prospective cohort study.

NPJ Breast Cancer 2022 Feb 17;8(1):21. Epub 2022 Feb 17.

Department of Oncology, Soroka University Medical Center and the Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.

Estrogen may have opposing effects on health, namely increasing the risk of breast cancer and improving bone health by increasing bone mineral density (BMD). The objective of this study was to compare dual-energy X-ray absorptiometry (DXA) BMD between women newly diagnosed with breast cancer and matched controls without breast cancer. Women newly diagnosed with breast cancer treated between April 2012 and October 2017 were prospectively enrolled. A control group was established of women with negative mammography or breast ultrasound, matched 1:1 by age, body mass index, parity, and the use of hormone replacement therapy. All those included had DXA BMD, and lab assessments at enrollment. Of 869 women with newly diagnosed breast cancer, 464 signed informed consent. Of the 344 who completed the study protocol, 284 were matched to controls. Overall, the mean age was 58 years. Compared to the control group, for the breast cancer group, the mean vitamin D level was lower (48.9 ± 19.0 vs. 53.8 ± 28.8 nmol/L, p = 0.022); and mean values were higher of total hip BMD (0.95 ± 0.14 vs. 0.92 ± 0.12 g/cm, p = 0.002), T score (-0.38 ± 1.17 vs. -0.68 ± 0.98, p = 0.002), and Z score (0.32 ± 1.09 vs. 0.01 ± 0.88, p < 0.001). Among the women with breast cancer, no correlations were found of baseline BMD with tumor size or grade, nodal involvement, or breast cancer stage. We concluded that women with newly diagnosed breast cancer tend to have higher BMD than women with similar characteristics but without breast cancer. This implies that BMD might be considered a biomarker for breast cancer risk.
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http://dx.doi.org/10.1038/s41523-022-00388-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8854387PMC
February 2022

Direct comparison shows that mRNA-based diagnostics incorporate information which cannot be learned directly from genomic mutations.

BMC Bioinformatics 2020 May 19;21(1):196. Epub 2020 May 19.

Shraga Segal Department of Microbiology, Immunology and Genetics, Ben-Gurion University of the Negev, Beersheba, Israel.

Background: Compared to the many uses of DNA-level testing in clinical oncology, development of RNA-based diagnostics has been more limited. An exception to this trend is the growing use of mRNA-based methods in early-stage breast cancer. Although DNA and mRNA are used together in breast cancer research, the distinct contribution of mRNA beyond that of DNA in clinical challenges has not yet been directly assessed. We hypothesize that mRNA harbors prognostically useful information independently of genomic variation. To validate this, we use both genomic mutations and gene expression to predict five-year breast cancer recurrence in an integrated test model. This is accomplished first by comparing the feature importance of DNA and mRNA features in a model trained on both, and second, by evaluating the difference in performance of models trained on DNA and mRNA data separately.

Results: We find that models trained on DNA and mRNA data give more weight to mRNA features than to DNA features, and models trained only on mRNA outperform models trained on DNA alone.

Conclusions: The evaluation process presented here may serve as a framework for the interpretation of the relative contribution of individual molecular markers. It also suggests that mRNA has a distinct contribution in a diagnostic setting, beyond and independently of DNA mutation data.
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http://dx.doi.org/10.1186/s12859-020-3512-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236449PMC
May 2020

Does Assessment Method Matter in Detecting Mental Health Distress among Ashkenazi and Mizrahi Israeli Women with Breast Cancer?

Health Soc Work 2020 May;45(2):101-109

Sheba Medical Center, Ramat-Gan, Israel.

Authors examined differences in assessment method (structured diagnostic interview versus self-report questionnaire) between ethnic groups in the prevalence of mood and anxiety disorders among women with breast cancer. A convenience sample of 88 Mizrahi (Jews of Middle Eastern/North African descent, n = 42) and Ashkenazi (Jews of European/American descent, n = 46) women with breast cancer from oncology units in three health centers across Israel participated in the study. Participants were within eight months of diagnosis. Participants completed the Hospital Anxiety and Depression Scale (HADS) and a structured diagnostic interview, the Mini-International Neuropsychiatric Interview (MINI). Approximately one-third (31.8 percent, n = 28) of participants were diagnosed with at least one mood or anxiety disorder based on the MINI. Significantly more Mizrahi participants (42.9 percent) were diagnosed with at least one mood or anxiety disorder, compared with their Ashkenazi counterparts (21.7 percent). Mean score on HADS was below the optimal cutoff score (≥13) among all participants, with no significant difference in mean score for emotional distress based on HADS between the two ethnic groups. The findings highlight the role of measurement variance in assessing mental health distress among women with breast cancer in general and among ethnic and racial minorities in particular.
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http://dx.doi.org/10.1093/hsw/hlaa004DOI Listing
May 2020

Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy.

NPJ Breast Cancer 2019 8;5:41. Epub 2019 Nov 8.

14Department of Oncology, Soroka University Medical Center, Beer Sheva, Israel.

The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10-year Kaplan-Meier estimates for distant recurrence/BC-specific mortality (BCSM) in this cohort. The analysis included 1365 patients. Distribution of RS results: RS 0-10, 17.8%; RS 11-25, 62.5%; RS 26-100, 19.7%. Corresponding CT use: 0, 9.4, and 69.9%. Ten-year distant recurrence rates in patients with RS 0-10, 11-25, and 26-100: 2.6% (95% confidence interval [CI], 1.1-6.2%), 6.1% (95% CI, 4.4-8.6%), and 13.1% (95% CI, 9.4-18.3%), respectively ( < 0.001); corresponding BCSM rates: 0.7% (95% CI 0.1-5.1%), 2.2% (95% CI, 1.3-3.7%), and 9.5% (95% CI, 6.0-14.9%) ( < 0.001). When the analysis included patients treated with endocrine therapy alone (95.5/87.5% of patients with RS 0-10/11-25), 10-year distant recurrence and BCSM rates for RS 0-10 patients were 2.7% (95% CI, 1.1-6.5%) and 0.8% (95% CI, 0.1-5.3%), respectively, and for RS 11-25 patients, 5.7% (95% CI, 3.9-8.3%) and 2.0% (95% CI, 1.1-3.7%), respectively. For RS 11-25 patients, no statistically significant differences were observed in 10-year distant recurrence/BCSM rates between CT-treated and untreated patients; however, this should be interpreted cautiously since the number of events was low and patients were not randomized. In conclusion, in node-negative ER+ HER2-negative BC patients, where treatment decisions in real-life clinical practice incorporated the RS, patients with RS 0-25 (~80% of patients, <10% CT use) had excellent outcomes at 10 years. Patients with RS 26-100 had high distant recurrence risk despite CT use and are candidates for new treatment approaches.
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http://dx.doi.org/10.1038/s41523-019-0137-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6841708PMC
November 2019
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