bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessment of circulating tumor cells in breast cancer patients undergoing neoadjuvant chemotherapy
Authors: Smerage J. B. , Hayes D. F. , Doyle G. V. , Terstappen L. W. , Brown M. E. , Schott A. F.
Published: March 2020

10079

Background: Circulating tumor cells (CTCs) are a valuable prognostic factor in metastatic breast cancer, suggesting that CTCs, if present, may be clinically useful in other breast cancer (BC) settings. This study prospectively evaluated CTCs before and after neoadjuvant chemotherapy (NACT) in patients with operable breast cancer. Methods: 7.5 or 30ml of blood were drawn in CellSave tubes from 26 Pts about to receive NACT (docetaxel + capecitabine followed by adriamycin + cytoxan) followed by surgery. CTC analysis is being performed at multiple time points. Data presented are from baseline (prior to first dose), post-NACT, and 3 months after surgery. CTCs were measured by immunomagnetic separation and automated fluorescent microscopy using the CellSearch System (Veridex/Immunicon Corp). Results: Baseline CTCs: For the first 11 pts CTCs were analyzed from 7.5ml of blood. 36% (4/11) had ≥1 CTC, 27% (3/11) had ≥2 CTCs. Of pts with detectable CTCs, the mean was 2.75 CTCs/7.5ml (range 1–4). To improve baseline sensitivity, 30ml blood was drawn from the subsequent 15 pts. One sample was not evaluable. 50% (7/14) had ≥1 detectable CTC and 29% (4/14) had ≥2 CTCs. Of pts with detectable CTCs, the mean was 3.0 CTCs/30ml (range 1–10). CTCs post-neoadjuvant therapy: All 26 pts had 30ml of blood drawn for CTC analysis. 27% (7/26) had ≥1 CTC, and 8% (2/26) had ≥2 CTCs. Using as threshold of ≥2 CTCs to define elevated, CTCs post-chemotherapy were compared to the pathologic complete response (pCR). Sensitivity was 10% (2 of 18 pts with residual disease had elevated CTCs). Specificity was 100% (0 of 7 pts with a pCR had elevated CTCs). This correlated to a positive predictive value of 100% and a negative predictive value (NPV) of 28%. CTCs 3 months after surgery: Of 21 pts analyzed, only one pt (5%) had a single CTC. Long-term follow-up blood collection is ongoing. Conclusions: CTCs are detectable in ∼30% locally advanced BC. All patients with CTCs after NACT had residual disease at surgery, and no CTCs were detected in patients with pCR. However, the absence of CTCs after NACT did not predict pCR. Pts will be followed to determine if CTCs correlate with recurrence and survival.

[Table: see text]
Pretherapeutic circulating endostatin levels in patients with gastric cancer
Authors: Hong S. H. , Woo I. S. , Jeon H. M. , Rho S. Y. , Koh S. J. , Lee M. A. , Byun J. H. , Kang J. H. , Hong Y. S. , Lee K. S.
Published: March 2020

10095

Background: Endostatin is an antiangiogenic fragment of collagen XVIII and is generated by tumor-derived proteases. The functional activity of circulating endostatin is currently unknown. This is the first report on serum endostatin in gastric cancer. Methods: A total of 111 patients with gastric cancer (52 metastatic patients and 59 patients undergoing gastrectomy without distant metastasis) were included in the study. Forty eight of 52 (92%) metastatic patients received systemic chemotherapy. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA and compared with the levels in 30 healthy controls. Data were analyzed using Student’s t-test and one-way ANOVA to compare means between groups, and using Spearman rank correlation to assess correlations between clinicopathologic factors and serum endostatin and VEGF levels. Survival curves were analyzed and compared using the Kaplan-Meier method and log-rank test. Results: Mean serum endostatin and VEGF levels were higher in gastric cancer patients than in healthy controls (endostatin, 69.8 ± 16.3 vs. 52.8 ± 6.0 ng/ml [P <0.001]; VEGF, 55.2 ± 7.5 vs. 31.9 ± 2.5 ng/ml [P <0.001]). Endostatin and VEGF levels were significantly higher in sera from metastatic patients than in sera from patients without distant metastasis (endostatin, 79.5 ± 17.9 vs. 61.3 ± 8.2 ng/ml [P <0.001]; VEGF, 57.4 ± 7.3 vs. 53.2 ± 7.2 ng/ml [P = 0.003]). There was a significant association between endostatin levels and the presence of distant metastases (r= 0.674; P <0.001). A correlation was also observed between serum endostatin and VEGF levels (r= 0.718; P <0.001). There was no significant difference in serum endostatin according to depth of tumor invasion, Lauren’s classification, differentiation, or regional lymph node status. A serum endostatin level higher than the median (78.14 ng/ml) was associated with a poor prognosis in metastatic gastric cancer (last follow- up at 42 months, median survival time 9 vs. 20 months [P=0.02]). Conclusions: In gastric cancer patients, serum endostatin levels are elevated and correlate with circulating VEGF levels as well as the presence of distant metastases. The endostatin level at diagnosis of metastatic gastric cancer may be useful for predicting survival time.

No significant financial relationships to disclose.
Breast self examination training and counseling as motivation strategies for breast awareness and participation in breast cancer screening programs
Authors: Artmann A. , Heyne M. , Kiechle M. , Harbeck N.
Published: March 2020

1027

Background: In Germany, the particpation rate in gynecologic cancer and the Bavarian breast cancer screening program is only about 30%. Therefore, the impact of counseling and raising confidence in breast self examination (BSE) by a structured BSE training on breast awareness, acceptance of screening offer, and participation rate was evaluated. For evaluation of the training quality, specified MammaCare data sheets and questionnaires were used. Method: Since 2003, 167 women (mean age 35 y; range 19–65 y; 61% ≥40 y) got intensive breast cancer counceling and were professionally trained in MammaCare BSE; 41% had positive breast cancer family history. In their beginner’s course, trainees got general BSE information, covering breast anatomy, breast symptoms, breast cancer screening and therapy. Participants practised BSE, after training on tactually accurate silicone breast models with simulated lumps in order to discriminate normal nodularity from lumps. After 3 months, the supervision sessions included BSE evaluation and - again - professional instruction. In a model exam false positive and negative findings were documented. In breast exams, performance technique and breast tissue coverage were assessed. At both initial sessions and after 12 months, questionnaires on BSE practice, experience, and compliance, cancer worry, acceptance and participation at cancer screening programs were evaluated. Results: Breast cancer worry, anxiety, and lack of information were the main reasons for program participation. Within 3 months after the base course, mean decrease of breast cancer worry was about 95%. Participation in gynecologic and breast cancer screening (≥40 y) more than doubled (94% and 86%). Even after 12 months, these numbers remain consistent. 80% of participants practice BSE monthly, and 46% reported changes in lifestyle regarding nutrition and obesity. Conclusions: Our approach emphasizes importance of self confidence and awareness for participation in cancer screening, also in women with breast cancer family history. Counseling, BSE re-evaluation and reinforcement are correlated with decreased breast cancer worry, a main barrier against participation in breast and gynecologic cancer screening.

[Table: see text]
Family information service (FIS) in a BRCA1 extended family
Authors: Lynch H. T. , Snyder C. , Lynch J. , Ghate S. , Thome S.
Published: March 2020

1028

Background: Considering that 10% of breast cancer is hereditary, it is essential to effectively educate hereditary cancer family members regarding the syndrome, cancer risk, genetic testing and cancer control options. Researchers at Creighton University (CU) have for many years provided family (group-oriented) information services (FISs) for hereditary cancer families. Methods: Such a session was held in collaboration with a genetic counselor in a community where many members of an extended hereditary breast-ovarian cancer family with a known BRCA1 mutation reside. Family members helped contact relatives and invited them to attend the full-day FIS at a local hospital. Informal presentations were provided by a CU geneticist/oncologist, a CU nurse counselor, and a local genetic counselor. Questions and comments were encouraged. An opportunity to provide a blood sample for genetic testing was offered. Results: Contacting relatives for the FIS identified more than 400 family members from previously unknown branches. Many attendees indicated this was their first opportunity to learn about this hereditary cancer syndrome, their risk, and recommended cancer control options. Patient-stated benefits of the FIS included increased communication of cancer risk among family members as well as with their physicians, motivation to become more vigilant with screening and health management and receipt of initial cancer risk education in a non-threatening venue. Conclusions: The FIS is a relatively simple, cost-effective educational cancer control program that increases communication among family members and their physicians, educates high-risk individuals and provides an opportunity for genetic testing which will ultimately provide an accurate cancer risk status and thereby alter health management and cancer control strategies.

No significant financial relationships to disclose.
Biology and prognosis of 1,685 recently diagnosed HER2-positive breast carcinomas
Authors: Ménard S. , De Placido S. , Scalone S. , Molino A. , Mottolese M. , Perrone F. , Querzoli P. , Sapino A. , Venturini M. , Viale G.
Published: March 2020

10501

Background: Understanding biology, prognosis and drug-sensitivity of HER2-positive breast cancer might help optimization of treatment of patients affected by this type of cancer. Most available studies are retrospective and suffer from the low frequency of this tumor subset. Methods: We conducted a large national retrospective/prospective study involving 1685 patients (cases) with HER2-positive (2+, 3+ score) primary breast carcinomas diagnosed in Italy in 2000/2001; for each case, in each participating center, a control was identified as the first consecutive patient with HER2-negative cancer (0, 1+ score). Results: In addition to the already known association with some pathologic parameters such as grade, hormone receptors, and ductal histotype, the four HER2 categories also displayed specific features, for example, a significantly higher frequency of p53-positivity among HER2–2+ tumors than in the other three categories, and a significantly lower frequency of lymphoid infiltration and desmoplasia, accompanied by a higher frequency of vascular invasion, in HER2–1+ as compared to HER2–0 tumors. Neither tumor size nor nodal involvement were associated with HER2 status. With a median follow-up of 4 yrs, the HER2-positive group showed a 20% relapse rate versus 14% in the HER2-negative group (p < 0.001). Analysis of relapse rates in the four HER2 categories indicated that only 3+ tumors show a significantly poorer prognosis, in both node-positive and node-negative subgroups; however, when patients who underwent invasive surgery are considered, the HER2–2+ patients also showed a significantly increased relapse rate as compared to negative cases, consistent with a stimulation of tumor cells by growth factors released at the time of surgery. Analysis of relapse rates according to type of therapy confirms the unresponsiveness to tamoxifen but sensitivity to chemotherapy, in particular taxanes, of HER2-positive tumors. Indeed, HER2-positive tumors were found to have a significantly better prognosis than HER2-negative when treated with taxanes. Conclusions: The present analysis conducted in a very large series of HER2-positive cases suggests innovative findings that can help optimization of treatment strategy for patients with HER2-positive breast cancer.

No significant financial relationships to disclose.
Epidemiology of triple negative breast cancer in Nigerian women
Authors: Adebamowo C. A. , Ogundiran T. , Akang E.
Published: March 2020

10504

Background: The epidemiology and immunohistochemistry of breast cancer in indigenous African populations is not well known with many studies relying on small case series. In this communication, we report a preliminary report from our study of the immunohistochemistry of breast tumors in Nigeria, highlighting the epidemiological characteristics of the “triple-negative” breast cancers and comparing these with non-triple negative breast tumors. Methods: 111 consecutive breast cancer patients presenting at the Oncology Clinic of the University College Hospital had tumor biopsied and demographic and epidemiological information collected. Standard histological and immunohistochemical analysis was done for ER, PR and HER2 status. Results: Most tumors were ER+ (65%, 69/106), PR+ (60%, 56/94) and HER2_ (91%, 82/90). 17% (13/76) of our patients had triple negative tumors. Patients with triple negative tumors were younger than those with triple negative (49.6 vs. 55.3 years p = 0.31), had shorter duration of symptoms (12.2 vs 20.7 months, p-value 0.18), later age at onset of menarche (17.4 vs 15.3, p-value = 0.25), lower BMI (27.2 vs 40.2, p-value = 0.01), greater height (157 vs 148 cm, p-value = 0.03), lower waist-hip ratio (0.84 vs 0.88, p-value = 0.16) and none of them had a positive family history of breast cancer. Conclusions: Contrary to previous reports, tumors in these African patients displayed immunohistochemical characteristics similar to those reported from Caucasian and other populations. Triple negative tumors were more likely to be associated with lower BMI and greater height, but more studies are needed.

No significant financial relationships to disclose.
Chemotherapy-related amenorrhea in women with early breast cancer: The effect of paclitaxel or dose density
Authors: Abusief M. E. , Missmer S. A. , Ginsburg E. S. , Weeks J. C. , Winer E. P. , Partridge A. H.
Published: March 2020

10506

Background: The effect of the addition of paclitaxel (T) to adriamycin and cyclophosphamide (AC), or dose density (DD, q2wk) on menstrual functioning in women with early breast cancer remains uncertain. Methods: We reviewed data from premenopausal women treated at Dana-Farber Cancer Institute and Brigham and Women’s Hospital who received adjuvant chemotherapy with either AC or AC-T from 1997–2005 for whom pre- and post-treatment menstrual data were available. A multivariable logistic regression model evaluating amenorrhea at 6 months or greater follow-up was conducted. Results: Of the 403 patients eligible for analysis, average age at diagnosis was 41 years (range 25–50); average weight was 67kg; 10% were smokers, 53% had never smoked; 24% were nulliparous. 60% of women received AC, 40% AC-T; 20% of women received DD therapy (either AC or AC-T); 72% received tamoxifen. The multivariable model adjusting for age, weight, gravity, parity, smoking, alcohol use, and tamoxifen use, revealed that risk of amenorrhea was not statistically different in patients receiving AC-T versus AC (OR = 1.45, 95% CI 0.78–2.69) or in patients receiving DD therapy versus standard (OR = 1.61, 95% CI 0.74–3.49). However, a planned future analysis including data from an additional 200+ patients may yield significant differences. Age directly correlated with risk of amenorrhea, OR = 1.40, 95% CI 1.30–1.50) for every year increase in age, and women receiving tamoxifen were more likely to be amenorrheic (OR = 1.99, 95% CI 1.05–3.79). Conclusions: The addition of T to AC or use of DD therapy does not appear to increase the likelihood of amenorrhea in follow-up. These findings may assist premenopausal women with breast cancer when making decisions at diagnosis and in follow-up.

No significant financial relationships to disclose.
Long-term effect in outcomes of intensified primary chemotherapy in poor prognosis LABC T4 patients: Results of a multicenter Italian study
Authors: Ionta M. , Atzori F. , Nonnis D. , Deidda M. , Contu A. , Farris A. , Catino A. , Palmeri S. , Minerba L. , Massidda B.
Published: March 2020

10518

Background: Recent data showed that anthracycline-based chemotherapy with increased dose-intensity improves clinical outcomes as compared to conventional regimens in adjuvant setting, particularly in high risk patients with HR negative tumors. Nevertheless dose-intensity in neoadjuvant setting remain controversial. The aim of this study was to evaluate the outcome between two different primary regimens and, furthermore, among soubgroups identified by HR status. Methods: Between 1996 and 2001, 72 consecutive LABC patients, (77% T4abc; 23% T4d; 88% axillary nodes involvement) median age 51 (29–70), ER neg 39%; PgR neg 71%, were treated with PEV regimen (cisplatin 50 mg/m2; epirubicin 100 mg/m2; vinorelbine 25 mg/m2) as primary chemotherapy. The regimen was delivered with different number of cycles and treatment intervals (3 wks × 4 cycles in the first 24 pts as PEV21 × 4; 2 wks × 6 cycles in the subsequent 48 pts as PEV14 × 6); the entire treatment in both groups lasted 12 weeks. All 72 patients received adjuvant CMF, RT and Hormonal treatment when indicated. Results: after a median follow up of 76 months (46–111), higher DFS and OS were observed in the intensified PEV14 × 6 group as compared to the counterpart (69% vs 42% p = 0.02 and 78% vs 58% p = 0.05 respectively). Statistically better DFS and OS were observed in the group ER/ PgR negative which received intensified PEV 14 × 6, whereas no statistically difference was found among ER/ PgR postive patients, regardless of the type of regimen. Conclusions: Our results suggest that primary intensified chemotherapy is associated with a better clinical outcome in poor prognosis LABC T4 patients,and that HR negative tumors benefit greatly from intensified regimen. Further prospective randomized studies are needed to confirm our data.

[Table: see text]

No significant financial relationships to disclose.
Proteomic analyses of normal and malignant breast tissue—Identification of a tumor-specific protein expression profile
Authors: Hudelist G. , Singer C. , Pischinger K. , Kaserer K. , Manavi M. , Kubista E. , Czerwenka K.
Published: March 2020

10524

Background: Gene expression analysis has become a promising tool in predicting the clinical course of malignant disease and the response to antineoplastic therapy. Suprisingly, only little is known about the protein expression pattern of human tumors. Recent advances in proteomic analysis allow to identify proteins of interest by their expression and/or modification pattern in 2D-PAGE rather than using the traditional approach of translating gene expression data. Methods: In order to identify a proteomic pattern that is characteristic for malignant breast epithelium, we performed differential 2D-PAGE analysis in sets of microdissected malignant breast epithelia and corresponding adjacent normal breast epithelia from 5 patients with invasive breast carcinoma. Results: Thirty-two protein spots were found to be selectively regulated in malignant epithelium, and were subjected to MALDI-TOF and/or immunoblotting for protein identification. Thirteen of the identified proteins had previously not been associated with breast cancer. The validity of these findings was confirmed by literature review and immunohistochemistry for identified proteins in an independent cohort of 50 breast cancer specimens. Conclusions: We here describe a proteomic analysis of matched normal and malignant epithelia from invasive breast carcinomas. This strategy leads to a better understanding of oncogenesis at an operational level and helps to characterize the malignant phenotype of individual tumors and thereby to identify novel targets for antineoplastic therapy.

No significant financial relationships to disclose.
Weight gain in breast cancer patients: Tamoxifen versus anastrazole
Authors: McGowan P. , Perry M. C. , Hewett J. E. , Ge B. , Sanfilippo K.
Published: March 2020

10544

Background: Weight gain is a common complaint among breast cancer patients, especially those taking tamoxifen. Aromatase inhibitors have been increasingly used in postmenopausal breast cancer patients, and are generally thought to have a more tolerable side-effect profile than selective estrogen receptor modulators (SERM’s). This study specifically addresses weight gain in patients on the SERM, tamoxifen, compared to patients on the aromatase inhibitor, anastrazole. Methods: Ninety-six outpatients with primary breast cancer of any stage received standard doses of adjuvant hormonal therapy. Seventy received tamoxifen (Group T) and 26 anastrazole (Group A). The nursing staff in the clinic weighed all patients at the time of diagnosis, at start of chemotherapy (if received), at start of hormone therapy, and at 3 month intervals for 12 months after starting hormone therapy. Data were gathered in a retrospective manner. Results: Demographic variables were compared between the two groups. In all patients, it was noted that increasing age was correlated with greater weight gain at 3 months after starting hormone therapy (p = 0.0257), but not at any other intervals. No other variables were significantly correlated with weight gain. In Group T, mean weight gain was clinically (>1.8 kgs) and statistically significant at 9 and 12 months (p = 0.0137, p = 0.0003). In Group A, mean weight gain was not clinically significant at any point. Using the Wilcoxon two-sample tests to compare groups T and A, it was shown that there was no statistically significant difference in weight gain between the two groups at any interval (see table). Conclusions: These results are consistent with previous studies that show significant weight gain in breast cancer patients on tamoxifen. This study failed to show a statistically significant difference in weight gain between patients on tamoxifen and patients on anastrazole. Group A did not have statistically significant weight gain at any interval after starting hormone therapy.

[Table: see text]

No significant financial relationships to disclose.
Tailored vinorelbine-capecitabine treatment in elderly metastatic breast cancer patients. A SICOG phase II study
Authors: Carreca I. , Iodice G. , D’Aiuto G. , Thomas R. , Costanzo R. , Licenziato M. , Petrillo A. , Maiorino L. , Frasci G. , Comella G.
Published: March 2020

10556

Purpose: To determine the antitumor activity of vinorelbine (VNR) and capecitabine (Xeloda) when given together, as first-line treatment, in elderly metastatic breast cancer (MBC) patients. Patients and Methods: MBC patients, aged >65 years, with no prior chemotherapy for metastatic disease, received capecitabine 1,000–1,250 mg/m2 d 1→14 and VNR 20–25 mg/m2 d 1–8, q3wk for a maximum of 6 cycles. Doses of VNR and Xeloda were alternately escalated in each patient (VNR 20→25 on 2nd cycle, Xeloda 1,000→1,250 on 3rd cycle), in absence or relevant hematologic/nonhematologic toxicity. Results: Forty-seven MBC pts., median age 72 (range: 66–82) were enrolled. Metastatic sites: visceral/other = 30/17. Adjuvant chemotherapy: Yes/no = 21/27. The doses were escalated as planned in 24/47 pts. To date, 41/47 pts. are evaluable for response. Three CRs and 25 PRs have been recorded, giving a 68% ORR (Visceral/other = 59%/85%). At a median follow-up of 15.3 months, 19 pts. have progressed, and 18 died, median PFS and OS being 14.1, and 20.3 months, respectively. Toxicity has been in general mild or moderate. Grade 3–4 neutropenia has occurred in 29% of pts., with only 2 episodes of neutropenic sepsis. Severe gastrointestinal side effects have been observed in only 2 pts., while severe mucositis and hand-foot syndrome have never occurred. Conclusions: VNR-Xeloda combination is highly active in elderly MBC patients. The adoption of an intrapatient dose escalation permits to minimize the risk of severe toxicity, without compromising efficacy. The accrual still continues until the planned sample size (60 pts.).

No significant financial relationships to disclose.
Megestrol acetate after aromatase inhibitor failure in metastatic breast cancer
Authors: Branco L. P. , Dienstmann R. , Bines J.
Published: March 2020

10572

Background: As aromatase inhibitors (AI) are now an essential component of the adjuvant hormonal treatment in breast cancer, it is important to define strategies after progression. Progestational agents have significant activity in endocrine-responsive breast cancer. This is the first report of megestrol acetate (MA) after AI failure. Methods: We have retrospectively reviewed the charts of all patients treated with MA for the last 2 years at the Instituto Nacional de Câncer, in Brazil. All the patients were postmenopausal and had metastatic breast cancer. The treatment sequence was as follows: tamoxifen ⋄ AI ⋄ MA. MA was given at a dose of 160 mg PO daily. Results: A total of 27 postmenopausal patients were treated between December 2003 and December 2005. Median age was 71 years (37–93). Seven patients had visceral metastases and 20 had bone, soft tissue or pleural disease. Eight patients are still on treatment. Median time to disease progression was 16 weeks (4–81), with no difference between those with or without visceral metastases: 17 and 16 weeks, respectively. Treatment was well tolerated and no patient discontinued therapy due to toxicity. There was no report of venous thromboembolism. Conclusions: Despite the limitations of a retrospective analysis, our results compare favorably with exemestane and high-dose estrogens in a similar setting. These agents have been studied in phase II trials (Lonning PE. JCO 18: 2234, 2000 and BCRT 67: 111, 2001) and showed time to progression of 15 and 18 weeks, respectively. A prospective trial of MA after AI failure is warranted.

No significant financial relationships to disclose.
The impact of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) on the decision-making process in breast cancer patients: The experience of Bologna’s S.Orsola-Malpighi Hospital
Authors: Sperandi F. , Fanti S. , Franchi R. , Martoni A.
Published: March 2020

10588

Background: 18F-FDG-PET is rapidly spreading “technology” in oncology. Its appropriate use and the clinical settings in which it can modify decision-making need to be defined. Methods: All the requests for 18F-FDG-PET issued by the Medical Oncology Unit are submitted to internal audit. The aim is to evaluate the impact of the information deriving from the test on the subsequent therapeutic strategy in breast cancer patients (pts). From July 2002 to July 2005, 195 18F-FDG-PET examinations were performed in 110 pts. Pt series have been subdivided according to disease stage or clinical setting: Group 1) NED during the follow-up 23 (11.8%); Group 2) suspected first recurrence 52 (26.7%) (included 20 cases with an isolated elevation of CA15.3 and/or CEA serum levels); Group 3) overt metastases: a) single lesion 10 (5.1%), b) multiple lesions with suspected disease progression 26 (13.3%), c) re-evaluation of non-progressive metastatic disease 84 (43.1%). Results: Overall, 18F-FDG-PET was positive in 112 (57.4%) cases: in Groups 1), 2), 3a), 3b) and 3c) positivity was 13%, 63.5%, 60%, 73.1% and 60.7%, respectively. As concerns those pts with an isolated marker serum level increase during the follow-up, 18F-FDG-PET was positive in 13 (65%) cases. Overall, the result of 18F-FDG-PET determined a therapeutic strategy change in 79 (40.5%) cases. This change consisted in a decision to start or re-start anti-tumor medical treatment in 46 (58.2%), to perform or exclude surgery or radiotherapy with a potentially radical purpose in 10 (12.7%), to continue follow-up or to stop treatment in 23 (29.1%). The change of strategy according to Groups 1), 2), 3a), 3b) and 3c) was 13%, 75%, 90%, 61.5% and 14.3%, respectively. Conclusions: A “clinical” approach to the use of 18F-FDG-PET in breast cancer pts allows us to change the decision-making in about 40% of pts. Clinical situations in which 18F-FDG-PET is more useful are in cases of suspected recurrence and oligometastatic disease.

No significant financial relationships to disclose.
Factors predicting tumor size at presentation in breast cancer patients
Authors: Rosenberg A. , Burke L. P. , Vos P. W. , Brinson M.
Published: March 2020

10609

Background: Early diagnosis of breast cancer improves prognosis. A high percentage of women at our institution present with large breast cancers. Using tumor board records, we investigated the potential covariates associated with tumor size at presentation, including age, race, marital status, and insurance status in order to identify populations at risk for presenting with late stage disease. Methods: Data were obtained from tumor board records of University Health Systems, Greenville, NC, a regional referral center in rural Eastern North Carolina. We analyzed data from patients presenting between 1999 and 2005. Relationships between tumor size at diagnosis and explanatory variables (marital status, age, ethnicity, and insurance status) were explored. Results: 1568 patients with breast cancer were identified of which 32% were African American (AA), 67% were White (W), and 0.6% other. 8.3% of patients had Medicaid; 27%, Medicare; 53.5%, private insurance; 3.4%, HMO; and 6.1% were uninsured. Tumor size was 0.01 to 25 cm and highly skewed so that statistical inferences were conducted on the log of tumor size. Tumors of >5 cm were found in 13.8% of AA women as compared to 6.4% of W women. Overall tumor size in AA women was larger than in W women (p-value = .0000). Marital status was not statistically significant (p-value = .5148). A linear regression model for log tumor size at time of diagnosis using explanatory variables marital status, age, ethnicity, and insurance status showed that only race (p-value = .0000) and age (p-value = .0004) were statistically significant. Older patients presented with somewhat smaller tumors. Most of the variability in log tumor size remained unexplained (r-squared = 4%). Conclusions: AA women were more likely to present with large tumors. While Medicaid patients had larger tumors, insurance status was not statistically significant in the linear regression model due to partial confounding of insurance and race: 20.8% of AA women were on Medicaid compared to 2.6% of W women.

No significant financial relationships to disclose.
Intraoperative radiotherapy impairs breast cancer cell motility induced by surgical wound fluid
Authors: Massarut S. , Baldassarre G. , Belletti B. , Colombatti A. , D'Andrea S. , Candiani E. , Perin T. , Reccanello S. , Roncadin M. , Vaidya J. S.
Published: March 2020

10611

Background: Most recurrences after breast conserving surgery for cancer occur in the tissues around the original tumour. Wound-fluid has been shown to induce proliferation of breast carcinoma cells. We investigated whether intraoperative radiotherapy (IORT) using the targeted intraoperative radiotherapy (Targit) technique changes the effect of surgical wound fluid on the behaviour of breast cancer cells. Methods: Preoperative peripheral blood serums (A) and wound fluid (B) (first 24 hours’s drainage) from 30 unselected patients undergoing breast conserving surgery with (14) or without (16) IORT using the Targit technique was collected, processed and stored at −80°C. The breast carcinoma cell lines (MDA-MB231, MDA-MB-45 and SKBR-3) were used to evaluate the activity of A and B on cell proliferation (MTT-FACS analysis) and motility (chemotaxis) and invasion (Matrigel). Results: Wound fluid stimulated cell proliferation, cell motility and cell invasion significantly more than the preoperative serum from the same patient. Targit did not influence the effect of wound fluid on cell proliferation. However, Targit abrogated the effect wound fluid on cell motility and cell invasion. Conclusions: This work demonstrates that wound fluid after surgery for breast cancer stimulates cancer cell growth and motility. Targit appears to significantly abrogate the effect on cancer cell migration and invasion. This outcome may confer more benefits than could be expected from the tumoricidal activity of radiotherapy, and may stimulate the development of novel peri-operative treatments directed at compensating the possible harmful effects of surgery.

No significant financial relationships to disclose.
Breast cancer in United Arab Emirates: Younger patients and more aggressive histology
Authors: Maarraoui A. M. , Utamachandani A. , Mattamona A. I. , Lazaro C. A. , Mathews L. S. , Saxen V. , Uttamchandani D. , Maarraoui Y. , Abdulatif H. , Attia N. M.
Published: March 2020

10612

Background: Mafraq hospital is the largest tertiary hospital in UAE. We tested the hypothesis that breast cancer patients in UAE present at a younger age and with more aggressive tumor histology Methods: This is a retrospective study on breast cancer cases seen at Mafraq hospital between 1/00 and 12/05. Intent to treat analysis was used. Total of 372 patients were seen, 48 patients (12.9%) were UAE citizens and 324(87.1%) were non-citizens, 370 females and 2 males. We categorized patients according to their age at time of initial presentation, menopausal status, TNM stage, tumor grade, lymphatic and vascular invasion, ER, PR, Her-2 neu and P53 status. Mode of surgery is also reported. Results: Mean patients age at time of initial presentation is 48 years. 230 (62%) of patients were pre-menopausal and 140 (38%) were post-menopausal. Tumor stages at initial presentation were as follows, stage 0: 7 patients (0.2%), stage I:59 patients (15.9 %), stage II: 180 patients (48.6%), stage III: 71 patients (19.2%) and stage IV: 53 patients (14.3%). Staging was not completed in 2 patients as they followed elesewhere. Vascular invasion was reported in 118 case, 58 (49.2%) were positive and 60 (50.8%) were negative. Lymphatic vessel invasion was reported in 106 case, 84 (79.2%) were positive and 22 (20.8%) were negative. Tumor grades were reported in 265 case and were as follows GI: 33 (12.5%), GII: 121 (45.6%), GIII: 109 (41.1%) and G IV: 2 (0.8%). Tumor hormonal status was reported in 270 case and were as follows: ER+ and PR+ in 94 case (34.8 %), ER+ and PR- in 31 case (11.5%), ER− and PR+ in 25 case (9.3%) and ER− and PR− in 120 case (44.3%). ER and PR were unknown in 102 case. Her2 neu studies were performed in 157 case. Out of those 77 (49%) were positive and 80 (51%) were negative. P53 mutation was studied in 132 patients 33 (25%) were P53 positive and 99 (75%) were P53 negative. 346 patient underwent surgery, 233 patient had modified radical mastectomy and 113 (32.7%) had breast conserving surgery. Conclusions: Breast cancer in UAE tends to occur at a younger age compared to western countries. The majority of our patients are pre-menopausal. Tumors have more aggressive histology and biology. Most tumors show vascular and lymphatic invasion. P53 and Her-2 neu over-expression is relatively high.

No significant financial relationships to disclose.
Detection of the AT1 and AT2 receptors of angiotensin II in malignant breast tumors and its correlation to cellular proliferation, hormonal profile and prognosis
Authors: Arrieta O. , Ceron-Lizarraga T. , Morales-Espinoza D. , Vizcaino G. , Gamboa A. , Pineda B.
Published: March 2020

10632

Background: Angiotensin II (ANG II) is the main effector peptide of the Renin-Angiotensin-Aldosterone System. ANG II has multiple physiologic effects and recent studies have demonstrated that is an angiogenic factor in non-tumoral experimental models. We demonstrated that malignant glioma cells express both receptors and the blockage of AT1 inhibits tumoral growth in vivo, and induces apoptosis. Studies on the ANG II receptors’ subtypes in adenocarcinoma of the breast in mice have demonstrated high expression of AT1; nevertheless, their expression in breast cancer hasn’t been studied. The objective of this study was to determine the presence of the ANG II receptors AT1 and AT2 in human breast cancer and their association to vascularity, cellular proliferation, hormone receptors; as well as to the disease free survival. Methods: Malignant breast tumors (n = 78) from patients who underwent surgery were collected between 2000 and 2004. Patients with neoadjuvant chemotherapy or radiotherapy were excluded. The AT1 and AT2 receptor expression was performed by RT-PCR and immunohistochemistry. The control samples were 8 breast fibromas. Results: The median age of patients was 54.7 years, the pathological stage included stage I (15.5%), II (65.5%) and III (18.9%). The patients underwent radical mastectomy in 61.4 % and conservative surgery in 39%. The median survival was 82 ± 5 months. AT1 and AT2 expression was found in 66% and 55%, respectively The coexpression of AT1 and AT2 receptors was positive-positive in 55% o and negative-negative in 16% of the tumors (p = 0.045). None of the benign tumors showed AT1 and AT2 expression (p = 0.01). The associated factors survival were stage (p = 0.03, log rank = 0.05) and differentiation grade. The AT1 receptor expression was associated with presence of estrogen receptors (p = 0.05), mitosis index (p = 0.05), cellular proliferation index (p = 0.01) and vascular density (p = 0.05). Conclusions: There is an important expression of the ANG II receptors AT1 and AT2 in breast cancer. AT1 and AT2 participate in cellular proliferation mechanisms of breast cancer and may play an important role in its biology, thus making them potential therapeutic targets.

No significant financial relationships to disclose.
Phase II trial of 4 cycles dose dense docetaxel (D) 100mg/m2 every 2 weeks with G-CSF support, followed by 3 cycles of 5-fluorouracil (F), epirubicin (E) and cyclophosphamide (C) every 3 weeks as neoadjuvant treatment of operable > 2cm breast cancer
Authors: Romieu G. , Bibeau F. , Culine S. , Gourgou-Bourgade S. , Guillemare C. , Kramar A.
Published: March 2020

10636

Background: Docetaxel is one of the most active chemotherapy agents used in breast cancer. Given the effectiveness of Taxotere in the treatment of metastatic breast cancer, it is now being extensively evaluated in the treatment of early stage disease. Recently, we initiated in our institution a study, which showed that the bi-weekly administration of 4 cycles of docetaxel was feasible with G-CSF (lenograstim) support. This phase II trial was initiated to evaluate the pCR rate of docetaxel as a single agent followed by FEC 100 in the neoadjuvant setting. Methods: Eligible patients (pts) with histologically proven breast cancer, measurable lesions >2 cm were scheduled to receive 4 cycles of chemotherapy with a day 1 bolus of (D) 100 mg/m2 every 14 days + corticoids for 3 days starting the day before first infusion as premedication and primary prophylaxis with G-CSF: followed by 3 cycles of a continuous infusion of F 500 mg/m2, E 100 mg/m2 and C 500 mg/m2 day 1 (FEC100). The primary endpoint was the pCR rate using the classification of Sataloff. Results: From 12/2003 to 12/2004, we treated 45 pts with median age 45 [25–63]. To date, 43 pts with WHO PS 0 were evaluable with T2: 22, T3: 19, T4: 2 pts and 18/21/5/1 N0/N1/N2/N3. Among 43 eligible pts, 2 stopped because of toxicity (after the 2nd and 4th cycles) and 1 patient refused to continue after 3 cycles. During the first treatment sequence with D, grade 3–4 toxicities (%pts): neutropenia (13), grade 3: cutaneous (24), myalgies (4), and arthalgies (2), and grade 2 neurotoxicity (31). During the second treatment sequence with FEC, grade 3–4 toxicities (% pts) were: neutropenia (95), grade 3: thrombocytopenia (5), myalgies (2), mucitis (2), grade 2 neurotoxicity (24). The conservative surgery rate was 67% and 3 pts needed a secondary mastectomy. The pCR rate was 50% (95% CI 34%– 66%) (26% T-A) among 42 evaluable pts. Conclusion: This regimen allows conservative surgery in more than half of all patients and we conclude from these findings that 4 cycles of dose-dense D followed by 3 cycles of FEC is an active induction regimen with a tolerable toxicity profile.

No significant financial relationships to disclose.
Efficacy and tolerability of biweekly paclitaxel combined with cisplatin in the treatment of metastatic breast cancer (MBC) patients previously treated with anthracyclines
Authors: Donat D. A. , Pesic J. , Trifunovic J. , Muzikravic L. , Tesanovic S. , Donat D. D.
Published: March 2020

10642

Background: Our aim was to assess the efficacy and tolerability of paclitaxel combined with cisplatin in the treatment of MBC patients previously treated with anthracyclines either as adjuvant treatment or as first-line chemotherapy for MBC. Methods: The study included 168 patients divided in two groups: 64 patients in group I who received adjuvant FAC and 104 patients in group II who received CMF as adjuvant therapy and FAC for MBC as first-line treatment. Participants received paclitaxel 90 mg/m2 on day 1 and cisplatin 60 mg/m2 on day 2 q/2w. Total number of cycles per patient was 3–9. Results: Evaluation was made after 3 cycles of chemotherapy. Obtained RR was: in group I, CR in 4 (6.26%), PR in 30 (46.87%), SD in 5 (7.81%), and PD in 25 (39.06%) patients, with ORR in 34 (53.13%) patients. In group II, the obtained results were: CR in 3 (2.88%), PR in 36 (34.6%), SD in 6 (5.77%), and PD in 59 (56.75%) patients, with ORR in 39 (37.49%) patients. Patients with CR received 3 more cycles and patients with PR received 3 or 6 therapies depending on the obtained results. Treatment evaluation of PR patients in group I after cycle 6 resulted with CR only in 1 (1.56%) patient and in group II showed CR in 2 (1.92%) patients. In those patients 3 more therapies were applied. Difference between the two groups in ORR is highly significant: p < 0.04. Hematological toxicity grades 3 and 4 in both groups were rare and similar. Conclusions: The application of biweekly paclitaxel combined with cisplatin in our patients’ population is efficacious with good tolerability. In group I the obtained results in ORR was 53.13%, which is statistically significantly (p < 0.04) better than in group II with ORR: 37.49%.

No significant financial relationships to disclose.
Is the Berg axillary lymph node categorization useful in the 3D Era
Authors: Saito A. I. , Vargas C. , Benda R. , Morris C. G. , Mendenhall N. P.
Published: March 2020

10643

Background: The Berg muscle-based categorization of axillary lymph node location has been used extensively by pathologists and surgeons to describe the extent of axillary node dissection in breast cancer patients, but its reproducibility with different arm positions and its utility in 3-D radiation treatment planning have not been tested. Methods: CT scans were obtained in 16 patients in 2 positions: historic position (HP), arms 90 degrees to the body axis; standard position (SP), arms above head. The volume, contents, and location of each Berg lymph node level (LNL) and the location of lymph nodes, surgical clips, pectoral muscles, and vascular structures relative to reference points were compared between the two scans. Results: Relative to T3, the LNL positions in SP were shifted from HP as follows: Level I, 23.1 mm anteriorly, p < 0.01; Level II, 7.5 mm medially, p = 0.04; Level III, 18.8 mm medially, p = 0.05. The pectoralis major and minor muscles were displaced medially (23.9 mm, p < 0.01 and 7.5 mm, p = 0.09) and anteriorly (18.2 mm, p < 0.01 and 11.2 mm, p < 0.01). At Level I, the axillary vessels (18.0 mm, p < 0.01), subscapular artery (25.4mm, p < 0.01) and lateral thoracic artery (8.4 mm, p < 0.01) were displaced anteriorly. With arm position change, lymph node position moved with vessel position rather than muscle position. Discrepancies were also observed in the number and location of lymph nodes (60%) and clips (66%) in given LNL’s between arm positions. Conclusions: Surgeons, radiologists, and radiation oncologists alike should be aware that lymph node position relative to muscle boundaries will vary significantly with arm position changes, making objective comparisons of information collected in different arm positions unreliable. This has significant implications for radiation treatment planning.

No significant financial relationships to disclose.
Does HER2/neu expression affect adjuvant treatment choices in routine clinical practice?
Authors: Pagani O. , Ruggeri M. , Rusca T. , Graffeo R. , Gallerani E. , Locatelli M. , Conti Beltraminelli M. , Longhi S. , Mazzucchelli L. , Goldhirsch A.
Published: March 2020

10667

Background: HER2/neu (HER2) amplification is a recognized independent prognostic and predictive factor. We retrospectively examined the correlation between HER2 expression and adjuvant therapy in patients (pts) with early breast cancer (EBC) at our Institution (IOSI). Materials and Methods: From January 2003, 326 consecutive pts with EBC have been treated at IOSI and all clinical and pathological data have been prospectively collected into a specifically designed data base (CARMA). HER2 expression was assessed by the c-erbB-2 oncoprotein antibody (NCL-L-CB11) in 309 pts (95%). FISH was not routinely performed. Endocrine responsiveness (ER+) is defined as Er and/or PgR expression by immunohistochemistry. Results: Overall, 58 pts (19%) had HER2+ disease. FISH was performed in 15 pts (24%) with doubtful antibody overexpression (2+) and did not confirm HER2 amplification in 4 cases (27%). Nodal involvement was not assessed in 1 HER2+ (2%) and in 12 HER2- pts (5%) due to advanced age. Menopausal status did not differ in HER2 positive and negative pts (29% and 27% premenopausal pts, respectively). The distribution of adjuvant chemotherapy (CT) according to tumour characteristics in HER2 positive and negative pts was as follows: An anthracycline-containing regimen was chosen in 88% of HER2+ pts receiving adjuvant CT as compared to 70% of HER2- pts. Outside of a clinical trial adjuvant Tamoxifen was given to 57% of HER2+/ER+ pts as compared to 75% of HER2−/ER+ pts. Conclusions: Overall, HER2+ pts showed less endocrine responsiveness (64% versus 88%) and more extensive nodal involvement (43% versus 30% with >3 positive nodes) as compared to HER2− pts. A greater proportion of HER2+ women received adjuvant CT, irrespective of other prognostic and predictive factors. In particular, a significant higher proportion of HER2+ pts with minimal nodal involvement (1–3 positive nodes) and ER+ disease received CT as compared to the equivalent HER2- subset (45% versus 26%, respectively).

[Table: see text]

No significant financial relationships to disclose.