bluuebunny/crossref_metadata_2025 huggingface dataset:
Differential response of primary cultures of breast carcinomas to lapatinib in an in vitro chemoresponse assay
Authors: Hancher L. M. , Ervin P. R. , Brower S. L.
Published: August 2020

1115

Background: Lapatinib (Tykerb) is a small molecule tyrosine kinase inhibitor that targets the intracellular domain of the epidermal growth factor receptor and HER-2, thereby inhibiting both growth and survival signaling pathways. Lapatinib is currently FDA-approved to treat HER-2-positive breast cancer previously treated with anthracycline and taxane therapies and trastuzumab. Due to the low population response rate of lapatinib, an integrated biomarker that can identify patients with an increased likelihood for response would be of great clinical utility. The current study describes an in vitro chemoresponse assay developed to predict sensitivity and resistance of primary cultures of human breast tumor specimens to lapatinib. Methods: The chemoresponse assay (ChemoFx) for lapatinib was developed using four different immortalized carcinoma cell lines (SK-OV3, BT474, MDA-MB-231, MCF7). In addition to cell lines, the chemoresponse assay was also performed on 55 first passage primary cultures of human breast carcinomas. All cultures were confirmed to contain keratin-positive epithelial cells using fluorescence immunocytochemistry. Cell lines and specimens were treated with a 10 dose concentration range of lapatinib for 72 hours and stained with DAPI; remaining live cells were counted on an inverted fluorescent imaging system. Resulting dose-response curves were analyzed and categorized as responsive, intermediate responsive, or non-responsive using a proprietary scoring algorithm. Results: All four cell lines (BT474, MDA-MB-231, MCF7, SK-OV3) were responsive to lapatinib treatment, with EC50 values of approximately 10 uM. Dose-response curves of the 55 primary breast cultures revealed that 9% of the specimens tested were responsive to lapatinib, 15% had an intermediate response, and 76% were non-responsive. These results are consistent with a reported clinical response rate of 10% for lapatinib. Conclusions: Initial results with the described integrated cell-based assay demonstrate that in vitro chemoresponse testing may be useful in predicting patient response to lapatinib. This type of in vitro biomarker is likely to increase the efficacy of the current chemotherapy decision-making process for oncologists and their patients.

No significant financial relationships to disclose.
Trastuzumab use and CNS metastasis in Medicare patients diagnosed with metastatic breast cancer (MBC)
Authors: Griffiths R. , Lalla D. , Brammer M. , Herbert R. , Doan J. , Danese M.
Published: August 2020

1123

Background: While trastuzumab was approved in 1998 for treating patients with HER-2-positive MBC, there is little information on its use in the Medicare setting. Methods: We used SEER-Medicare data to examine patterns of trastuzumab use in women diagnosed with MBC . An index date was defined as either the date of diagnosis (stage IV) or of first distant recurrence (stage 0-III). Included patients were diagnosed in 2000–2002, and had their first claim for trastuzumab between their index date and December 31, 2005, the end of the observation period. Patients were divided into those who received trastuzumab as part of their first treatment following their index date (Group A), and those who began trastuzumab after at least one course of chemotherapy (Group B). Chemotherapy agents were grouped into antimicrotubule (vinorelbine, docetaxel, paclitaxel, vincristine), anthracycline (doxorubicin, epirubicin), cyclophosphamide, other, and unknown. Results: 281 patients met the inclusion criteria. Overall, the median (mean) time from the index date to initial chemotherapy and/or trastuzumab treatment was 35 (94) days (range 1–1,587 days). The average duration of trastuzumab use (first to last administration) was 371 days (median 239), during which patients averaged 2.3 trastuzumab claims per month. There were 192 (68%) patients in Group A. The median (mean) time from diagnosis to initial treatment in Group A was 34 (94) days. 64 (33%) received trastuzumab alone, and 121 (63%) received trastuzumab with an antimicrotubule. In Group B (89 patients), the median (mean) time to initial chemotherapy was 41 (92) days. 36 (40%) received anthracycline and/or cyclophosphamide based therapy, 22 (25%) received an antimicrotubule without either an anthracycline or cyclophosphamide. The median (mean) time from initial chemotherapy to initial trastuzumab therapy was 233 (368) days. At that time, 29 (33%) received trastuzumab alone, and 54 (61%) received trastuzumab plus an antimicrotubule. Conclusions: To our knowledge, this is the first study to describe patterns of trastuzumab use in Medicare. When used for metastatic breast cancer, trastuzumab was most often provided soon after diagnosis as part of initial treatment, and usually with an antimicrotubule agent.

[Table: see text]
Relationship and prognosis of hospho-Akt and CD44v6 in breast cancer
Authors: Yu P. , Zhou L. , Song K. , Li K.
Published: August 2020

1126

Background: The purpose of this study was to investigate the relationship between pAkt and CD44v6 expression of breast cancer after surgery. We also evaluated the expression patterns and predictive value of pAKT and CD44v6 in breast cancer tissues. Methods: Expression of pAkt and CD44v6 protein was detected using immunohistochemistry in 98 patients. The correlation between the expression of pAkt, CD44v6, and other disease-related characteristics with treatment outcome was investigated. Kaplan-Meier survival analysis and Cox regression were used to observe the correlation between variables and the prognostic value. Results: Of all these 98 cases, 37 cases (37.8%) were observed as positive for pAkt expression, and there were 25 cases (51.0%) pAKT positive expression in the lymph node (+) and 15 (30.6%) in lymph node (-) of 49 cases. pAkt expression had no significant difference in node-positive group and node-negative group. We examined the relationship between pAKT and HER2 expression, pAkt expression was positively correlated with HER-2 expression (p = 0.009). A statistically significant difference in positive staining for pAkt was observed between CD44V6-positive and CD44V6-negative tumors (p = 0.016). CD44v6 positive tumors showed a statistically very highly significant association between node-positive and node-negative (p = 0.013). For prognosis value, a week relationship was observed between pAkt and OS, but DFS was inversely associated with pAkt staining intensity (p = 0.061, p = 0.004). There had a statistical correlation between CD44v6 overexpression and OS and DFS (p = 0.026 and 0.006 respectively). Univariate analysis revealed that lymph node status and CD44V6 were significantly associated with decreased OS and DFS, but there had no significant difference between variables and OS and DFS by multivariate analysis. Conclusions: Our data suggested that there had a intensive relationship between pAKT and CD44v6 expression in breast cancer tissues. We demonstrated that both pAkt and CD44v6 were significantly assiociated with a decreased OS and DFS in breast cancer patients. pAKT and CD44v6 overexpressed in cancer cells may be sensitive markers for predicting the treatment outcome in breast cancer patients.

No significant financial relationships to disclose.
Dose-escalating study of continuative low dose of oral vinorelbine in patients with advanced breast cancer
Authors: Felici A. , Russillo M. , Di Segni S. , Fabi A. , Ferretti G. , Carlini P. , Contestabile M. , Nuvoli B. , Sperduti I. , Cognetti F. , Papaldo P.
Published: August 2020

1128

Background: Low and continuative dose of antineoplastic drugs has been shown to have an antiangiogenic activity. The rapid absorption and relatively short half-life of the oral formulation of vinorelbine are favorable pharmacokinetic characteristics to test a continuative low-dose schedule. Methods: Patients with measurable metastatic breast cancer were treated with escalating dose of oral vinorelbine from 50 mg/m2 per week to 90 mg/m2 per week until progressive disease or unacceptable toxicity. These patients were administered one third of the total weekly dose 3 times per week, every other day. A pharmacokinetic analysis was planned at the first 3 weeks of drug assumption. Results: Of twenty-two patients included in the study, 3 were treated at 50 mg/m2/w (level 1), 5 at 60 mg/m2/w (level 2), 3 at 70 mg/m2/w (level 3), 8 at 80 mg/m2/w (level 4), and 3 at 90 mg/m2/w (level 5); we are still enrolling patients at this level. The median age was 59 years (range 23–75). The median number of prior lines of chemotherapy and hormonal therapy was 2 (range 0–4 for CT and 0–5 for OT). Fifteen of 22 patients had visceral metastasis. No dose-limiting toxicities have been observed until now. The main toxicities were: asymptomatic neutropenia grade 4 in two patients (1 in level 4 and 1 in level 5), asthenia grade 3 in 7 patients (1 at level 1, 2 at level 2, 1 at level 3, 3 at level 4), neurotoxicity grade 3 in two patients (one at level 2 and one at level 4). One patient experienced an intestinal sub-occlusion and hospitalization was required with no permanent side effects. One patient had a partial response, five a stable disease, fourteen progressed and two are not evaluated yet. At 1 year, five of the twenty evaluable patients are died by disease. Samples of twenty patients were collected for pharmacokinetic analysis that will be presented at the meeting. Conclusions: The continuative split 3 times per week oral vinorelbine is feasible, and at 90 mg/m2/w we have not reached yet the maximum tolerated dose.

No significant financial relationships to disclose.
In situ protein expression of RRM1, ERCC1, and BRCA1 in metastatic breast cancer patients treated with gemcitabine-including chemotherapy
Authors: Metro G. , Zheng Z. , Fabi A. , Mottolese M. , Monteiro A. N. , Vici P. , Boulware D. , Lara Rivera S. , Cognetti F. , Bepler G.
Published: August 2020

1129

Background: Ribonucleotide reductase 1 (RRM1) is a determinant of gemcitabine efficacy in non-small cell lung cancer (NSCLC) and pancreatic cancer. We investigated the tumoral levels of RRM1 in a population of metastatic breast cancer (MBC) patients treated with gemcitabine-based regimens. The protein levels of the excision repair cross-complementation group 1 (ERCC1) and breast and ovarian cancer susceptibility gene 1 (BRCA1) were also measured. Methods: Fifty-five patients were treated and followed prospectively from September 2004 to December 2007. Treatment consisted of gemcitabine plus a taxane in 46 patients and gemcitabine plus pegylated liposomal doxorubicin in 9 patients. RRM1, ERCC1, and BRCA1 were determined by automated in situ protein quantification (AQUA v1.6) on a tissue microarray containing triplicate tumor specimens. Results: The average scores for RRM1, ERCC1, and BRCA1 ranged from 245.6–2, 774.1, 74.0–410.3, and 54.4–1, 833.1, respectively. A statistically significant correlation between the levels of expression of all three markers (Spearman's rho > .36; P < 0.007) was observed. There was no significant association between RRM1, ERCC1, or BRCA1 levels and disease response, progression free survival, or overall survival. Conclusions: In tumor specimens from patients with MBC, RRM1, and BRCA1 had a range of expression and pattern of distribution that makes these markers potentially suitable for clinical decision making. In contrast, the relatively narrow range of ERCC1 expression might signify that ERCC1 protein levels are not useful predictors of platinum efficacy in MBC. Consistent with what has been shown in NSCLC, RRM1, ERCC1, and BRCA1 levels were significantly correlated, suggesting that the coexpression of such DNA repair proteins may be universal to epithelial malignancies. The lack of correlation between marker levels and clinical outcome may be explained by the specific chemotherapy combinations used.

No significant financial relationships to disclose.
Safety of a novel capecitabine dosing schedule when combined with lapatinib in patients with HER2-positive metastatic breast cancer refractory to trastuzumab
Authors: Traina T. A. , Theodoulou M. , Feigin K. , Patil S. , Geneus S. , Modi S. , Fornier M. , Lake D. , Norton L. , Hudis C.
Published: August 2020

1131

Background: Capecitabine (C) is active in breast cancer and is usually dosed for 14 days (d) followed by a 7d rest (14 - 7). We described a mathematical method which predicts the optimal schedule for C to be 7d followed by a 7d rest (7 - 7) (Norton et al, Amer Assn Can Res. 2005). The MTD of C(7 - 7) is 2,000mg BID (Traina et al, J Clin Oncol. April 2008). Lapatinib (L) improves time to progression when added to C(14 - 7) in patients (pts) with HER-2-positive (+) metastatic breast cancer (MBC) that progressed after trastuzumab (T). To optimize this effective combination, we are testing C(7 - 7) + L in a phase II trial. Methods: Eligible pts have measurable, HER-2(+) MBC that has progressed after T. HER-2(+)=IHC 3+ or FISH>2. Pts have normal LVEF by MUGA, ECOG performance status (PS) <2 and normal organ function. <3 prior chemotherapy (CRx) regimens are permitted. Prior fluoropyrimidine is excluded. Therapy (tx) consists of C (2,000 mg BID, 7 - 7) and L (1,250 mg, daily). Cycle length = 4 wk. Pts are evaluated for toxicity q4 weeks (wk), for response q12wk; LVEF by MUGA q12wk. Primary endpoint: response rate (RR). Secondary endpoints: toxicity, stable disease >6 months, PFS. Using a Simon optimal 2-stage design, with alpha = 10%, power = 90% to discriminate between RR 10% and 25%, 21 pts will be accrued to the first stage. If >2 pts respond, 29 additional pts will be enrolled. If >7/ 40 pts respond, then C(7 - 7) + L will be considered worthy of further study. Results: As of January 5, 2008, 6 pts are enrolled and evaluable. Median (med) age 64 yrs (42–71), med ECOG PS 1 (0–1), ER/PR(+) 3, HER-2(+) 6, sites of MBC: bone (2), viscera (4), soft tissue (5). Med baseline LVEF 62% (51–68%). Prior tx: Adjuvant: CRx (5), hormone tx (3), T (3); MBC: CRx (2), hormone tx (1), T (3). After a med of 3 cycles (1–4), there were no grade 3, 4, or 5 events. Tx-related toxicity is: Gr 2 fatigue (1); Gr 1 AST (4), diarrhea (3), ALT (2), vomiting (1), hand-foot (1), fatigue (1). No withdrawls due to reduced LVEF. Two pts evaluable for response: PR = 1, SD<6 mo = 1. Conclusions: Capecitabine (7 - 7) + lapatinib appears well tolerated compared to C(14 - 7)+L (Geyer et al). Additional safety and efficacy data is anticipated prior to this meeting.

[Table: see text]
Combination of trastuzumab, oxaliplatin, and docetaxel as first-line treatment in HER2-positive metastatic breast cancer patients: First-step results of a phase II trial (HOT trial)
Authors: Amoroso D. , Donati S. , Valsuani C. , Puccetti C. , Rondini M. , Siclari O. , Tartarelli G. , Giannessi P. , Falcone A. , Camerini A.
Published: August 2020

1132

Background: The addiction of trastuzumab to standard chemotherapy has improved the outcome of HER-2-positive metastatic breast cancer (MBC) pts. Oxaliplatin and docetaxxel are among the most active agents in MBC pts pretreated with anthracyclines. In vitro studies showed synergistic effect of the combination. We investigated the feasibility and the safety of the 3-drug combination given as first line chemotherapy (CT) in HER-2-positive MBC. Methods: HER-2-positive MBC pts were prospectively enrolled to receive a first-line treatment consisting of trastuzumab 8 mg/kg loading dose iv (followed by 6 mg/kg) on day 1, docetaxel 75 mg/sqm iv on day 1, and oxaliplatin 70 mg/sqm on day 2 every 21 days. All pts received peg-filgrastim 6 mg on day 3 to prevent bone marrow toxicity. Pts received up to 9 cycles of CT. Primary end points were overall response rate (ORR) (according to RECIST criteria), clinical benefit (CB), and tolerability. Cardiac function was evaluated by echocardiography at baseline, each 3 courses and at the end of treatment. Results: To date, 13 pts have been enrolled (median age 59 yrs [range 34–70]; ECOG PS 0) representing the first-step accrual according to Minimax design. Ten pts had previously received anthracyclines as adjuvant treatment and 11 pts presented with visceral metastasis. All pts received at least 6 cycles of treatment with 7 pts continuing up to 9 cycles. Response and toxicity data are available for all pts. Two pts experienced CR, 7 pts PR, and 4 pts showed SD (lasting more than 6 months in 3 cases) with an ORR of 70% and a CB of 100%. No pts progressed during treatment. No grade 4 toxicity was observed. Most common grade 3 toxicities were diarrhea (18%), nausea/vomiting (22%), mucositis (11%). In particular, 2 episodes of febrile neutropenia were reported and no grade 4 haematologycal toxicity was observed. No significative reduction of LVEF were reported. Conclusions: The combination of trastuzumab, oxaliplatin, and docetaxel (HOT combination) showed promising activity and was well tolerated as first-line treatment in pts with HER-2-positive MBC. Peg-filgrastim profilaxis improved safety profile.

No significant financial relationships to disclose.
A phase II study of GW786034 (pazopanib) in patients with recurrent or metastatic invasive breast carcinoma: Results after completion of stage I: A trial of the Princess Margaret Hospital Phase II Consortium
Authors: Taylor S. K. , Chia S. , Dent S. , Clemons M. , Grenci P. , Wang L. , Oza A. M. , Ivy P. , Pritchard K. , Leighl N.
Published: August 2020

1133

Background: Pazopanib, an oral small molecule inhibitor of VEGFR, PDGFR, and KIT, has demonstrated activity in phase I, with a recommended phase II dose of 800 mg/d (Hurwitz H et al, J Clin Oncol. 2005;23[16 suppl]:3012.1). We evaluated the activity of single agent pazopanib in recurrent or metastatic breast cancer (MBC). Methods: In this 2-stage design, patients with recurrent or MBC received pazopanib 800 mg/d. The primary endpoint was objective response rate (ORR) of 20%. Response in 3 out of 18 patients was required to go to stage 2. Treatment was continued until progression. Results: 21 patients entered stage 1; 67% were ER positive and all were HER-2-negative. Prior lines of chemotherapy were 1 in 76% and 2 in 14%. Of the 19 evaluable patients, 2 patients remain on treatment. 14 (74%) stopped due to progressive disease, 2 (10%) due to adverse events, and 1 (5%) due to patient request. Best response was partial response (PR) in 1 (5%), stable disease (SD) in 11 (58%), and progressive disease in 7 (37%). Clinical benefit rate (CR, PR, or SD for ≥ 6 months) was 26%. Median time to progression (TTP) was 3.7 months (95% C.I. 1.7 months - not reached). 9 out of 18 patients (50%) with measurable target lesions had some decrease in target lesion size. Estimated progression-free survival at 3 months was 55%, and 28% at 6 months. Adverse events were grade 3/4 elevations in AST (14%) and ALT (10%), and grade 3 hypertension and neutropenia (14% each). Other common events were grade 1/2 lymphopenia, neutropenia, diarrhea, fatigue, skin hypopigmentation, hypertension, nausea, vomiting, anorexia, and headache. Conclusions: Pazopanib is well tolerated and demonstrates activity in pretreated breast cancer. While the target ORR of 20% has not been met, rates of SD and TTP are comparable to other active agents in this setting, and therefore pazopanib may be an interesting agent for future studies in breast cancer.

[Table: see text]
A prospective study of reproductive factors, hormone use, and risk of lung cancer in postmenopausal women
Authors: Baik C. S. , Strauss G. M. , Feskanich D.
Published: August 2020

1501

Background: There has been increased interest in understanding the role of hormonal factors in lung cancer (LC) in women with the observation that it exhibits different epidemiologic patterns and treatment response when compared to men. However, results of published studies have been inconsistent, possibly due to inadequate smoking adjustment. Methods: We prospectively examined the associations between reproductive factors, exogenous hormone use, and LC incidence in 106,574 postmenopausal women in the Nurses’ Health Study. Participants completed biennial questionnaires which included updated smoking history. We assessed age at menopause, age at menarche, type of menopause, parity, postmenopausal hormone (PMH), and oral contraceptive use. Cox proportional hazards modeling was used to estimate the relative risks (RR) of each exposure, adjusted for smoking status, number of cigarettes, time since quitting, age of initiating smoking, fruit/vegetable intake, body mass index, and environmental smoking exposure. Results: We identified 1,565 LC cases during follow up from 1984 to 2004. Parity was associated with decreased LC risk in never smokers (RR = 0.54, 95% CI 0.31–0.96) but increased risk in current smokers (RR = 1.44, 95% CI 1.03–2.02). No association was seen in former smokers. Also, younger age at menopause was associated with higher LC risk in women with natural menopause (p-trend = 0.016). PMH use was not associated with LC incidence. The RR for current PMH users was 1.01 (95% CI 0.87–1.17) and for past users was 0.95 (95% CI 0.82–1.1). No significant association was seen when assessed by duration of PMH use, time since last use, or type of PMH. However, past use of oral contraceptives for greater than 5 years was associated with increased LC risk (RR = 1.2, 95% CI 1.03–1.41). Conclusions: These results suggest that there may be an association between hormonal factors and LC development, and further suggest that the mechanism may differ in smokers versus lifelong never smokers.

No significant financial relationships to disclose.
Occult ovarian cancers at the time of risk-reducing salpingo-oophorectomy in a prospective cohort of BRCA1/2 mutation carriers
Authors: Rebbeck T. R. , Friebel T. M. , Domchek S. M.
Published: August 2020

1508

Background: Risk-reducing salpingo-oophorectomy (RRSO) is widely used for cancer risk reduction in women with BRCA1 or BRCA2 (BRCA1/2) mutations. Occult ovarian cancers (OOC) detected at the time of RRSO have been reported, but there is wide variability in reported prevalence rates. Methods: We evaluated a prospective cohort of 647 women from 18 centers who underwent RRSO between 2001 and 2007 after a positive genetic test for disease-associated BRCA1/2 mutations. We estimated the prevalence of OOC. Results: Mean follow-up from genetic testing to RRSO was 1.01 years. OOC was detected in 16 of 647 women (2%). The mean age of women in whom OOC was detected was 51.7 versus 46.6 in women undergoing RRSO in whom OOC was not detected (p = 0.017). Twelve of the 16 OOCs (75%) were diagnosed in women with a BRCA1 mutation. Two OOCs were detected on RRSO prior to age 40, both in BRCA1 mutation carriers. Thirty eight percent of women with OOC had stage I cancer, as opposed to 10% of women in the PROSE database diagnosed with ovarian cancer outside of screening (p = 0.006). Among the 283 women in whom pathology reports were available for central review, 71% of RRSO were performed at the respective PROSE sites (i.e. major genetic referral centers), while 29% of RRSO were performed at local sites (i.e. community hospitals). Ovarian and fallopian tube tissues removed at RRSO at major genetics referral centers were significantly more likely to have been examined in toto compared to specimens obtained at nonreferral centers (76% vs. 24%, p < 0.001). Conclusions: RRSO reduces cancer risk and mortality in BRCA1/2 mutation carriers. Our results confirm that OOC is present at RRSO in BRCA1/2 mutation carriers, and suggest that OOC are more frequent after age 40 and are of a more favorable stage than cancers found outside the context of RRSO. Despite the fact that we examined surgeries after 2001, an unacceptably high proportion of pathologic examinations did not adequately examine ovaries and fallopian tubes obtained at RRSO. Failure to perform adequate pathological examination may overlook OOC and have clinical consequences for women undergoing RRSO.

No significant financial relationships to disclose.
Parent perceptions of offspring responses to parental communication of BRCA1/2 test results
Authors: Bradbury A. R. , Patrick-Miller L. , Egleston B. , Sands C. , Feigon M. , Pawlowski K. , Ibe C. , Daly M. , Olopade O. , Daugherty C.
Published: August 2020

1511

Background: Many BRCA1/2 mutation carriers report sharing their genetic test results with their minor children. The impact of this communication on offspring remains unknown. Methods: 163 parents who had BRCA1/2 testing completed qualitative interviews regarding their experiences with communication of their genetic test results to offspring. Descriptive responses were coded and response proportions utilized to summarize results. We used multiple regressions fit by GEE to test associations with disclosure. We controlled for parent mutation status in each regression. Results: 163 parents (52 BRCA1/2 mutation carriers) reported on 323 offspring 5 to 25 years old at the time of parent genetic testing. 107 (66%) parents reported disclosing to at least one offspring. Child age (p < 0.001) and parent cancer history (p = 0.004) were positively associated with disclosure. Parents without a BRCA1/2 mutation were more likely to communicate test results than parents with a mutation (p = 0.007). Among parents who disclosed, few (14%) reported they perceived their offspring to have had an initial negative affective or behavioral response. Others (13%) reported offspring concern for self and family. Reports of initial negative responses and concern were more frequent among parents with a mutation or a variant of uncertain significance. Many parents reported that the communication had no significant impact (39%) or a positive impact (36%) on their offspring. Conclusions: Many parents report sharing BRCA1/2 test results with their offspring. Parent self-reports suggest that they do not perceive most offspring to experience adverse reactions to this communication. Self-reports suggest that offspring learning of a BRCA1/2 mutation or a variant of uncertain significance may be more susceptible to initial negative reactions. Further research is necessary to explore psychosocial and behavioral responses to learning of hereditary risk during childhood and adolescence, and to inform the development of interventions to optimize adaptive response.

No significant financial relationships to disclose.
Characteristics of young women enrolled in a high-risk breast cancer screening program
Authors: Tierney S. , Delli Carpini J. C. , Gemignani M. L.
Published: August 2020

1512

Background: Young women at higher risk for breast cancer may benefit from enrollment in a dedicated surveillance program to ensure that their unique needs for examination, imaging, and risk modification are met. Though these programs do exist, little information is known about their effectiveness. In this pilot study, we sought to characterize the patients enrolled in our high-risk screening program. Methods: The Special Surveillance Breast Program (SSBP) at the Memorial Sloan-Kettering Cancer Center (MSKCC) was initiated in 1992 and enrolls patients in four categories: known and probable genetic mutation carriers, atypia, LCIS, and positive family history. Data is collected prospectively in an IRB-approved database and reviewed retrospectively. Patients enrolled from 1992 to March 2008 were included. Inclusion criteria included age under 40 and at least one follow-up visit. Data was validated with the patients’ medical records. Results: Four hundred and thirteen patients met inclusion criteria. The median age at enrollment was 33. The median duration of enrollment was 41 months. Defining continued participation as having a follow up visit in 2008, 193 patients (48%) were retained. At enrollment, 247 patients (60%) had ever undergone screening breast imaging. Of these, 216 patients (52%) had undergone screening in the past 2 years. At the most recent visit, 394 patients (95%) had ever undergone screening breast imaging and 376 patients (91%) had undergone screening in the past 2 years. Of the patients who had not had any radiologic screening, 18 patients (78%) were under the age of 35 at the most recent visit. Two hundred and ninety one patients (70%) reported performing self-breast exams. Two patients were diagnosed with cancer during their participation. An additional six patients underwent prophylactic surgery at MSKCC. Conclusions: Enrollment in a high-risk screening program was associated in an increase in any utilization of radiologic screening from 60% to 95%. It is unknown how this would compare to similar high-risk populations not enrolled in any program. Considering their voluntary enrollment and return for follow-up, these women are likely highly motivated regarding their health care. Further prospectively collected survey data from patients, including those who did not return after their initial visit, is planned.

No significant financial relationships to disclose.
Adherence to extracolonic cancer screening in Lynch syndrome kindreds
Authors: Stadler Z. K. , Stern R. , Devlin V. , Glogowski E. , Kauff N. , Offit K. , Hurley K.
Published: August 2020

1513

Introduction: In addition to colorectal cancer (CRC), Lynch syndrome (LS) patients are at increased risk of extracolonic malignancies including endometrial (EC), ovarian (OC), upper gastrointestinal and urothelial tract cancers. Although the efficacy of extracolonic cancer screening in LS has not been clearly demonstrated, multi-organ screening is routinely recommended for LS patients (Lindor et al., JAMA 2006). Anecdotal evidence suggests that adherence to such screening may be inferior to CRC screening. Methods: 35 adults, identified in the context of genetic counseling and testing (GCT) as being from LS kindreds, were given recommendations for multi-organ screening and enrolled on a prospective follow-up study. For participants with relevant organs at risk, these included colonoscopy, urine cytology, transvaginal ultrasound (TVUS), CA-125 level and endometrial sampling all to be performed at least annually. Adherence with screening, perceived risk of cancer subtype and future intentions regarding screening were evaluated at least 12 months after GCT. Results: Median age at time of GCT was 44, 66% were female and 69% were diagnosed with a LS- related cancer prior to GCT (15 CRC; 9 EC). At time of follow-up, 89% of patients without CRC had a colonoscopy within the year. Among women at-risk for OC, 25% had TVUS and 38% had CA-125 level within the year. Among women at risk for EC, 22% had TVUS and 22% had endometrial sampling within the year. Of all participants, 40% had urine cytology within the year. Of participants with relevant organs at-risk, 72%, 33%, 75% and 12% reported their risk of developing CRC, EC, OC, and urothelial tract cancer, respectively, as “moderately”, “very” or “extremely” high. Of patients with previous colonoscopy, 93% had definitive intentions to continue on schedule screening. However, only 68%, 50%, 60% and 50% of patients who underwent previous urine cytology, TVUS, CA-125 or endometrial sampling, respectively, had definitive intentions of continuing on schedule screening. Conclusions: Adherence with extracolonic cancer screening in LS kindreds is poor and patients persistently underestimate their extracolonic risk despite GCT. Possible interventions should be aimed at better educating patients about extracolonic cancer risk and importance of on-going surveillance.

No significant financial relationships to disclose.
Feasibility of thermal infrared imaging screening for breast cancer in rural communities of Southern Mexico: The experience of the Centro de Estudios y Prevencion del Cancer (CEPREC)
Authors: Gutierrez-Delgado F. , Vazquez-Luna J. , Venegas-Hernandez L. , Terrazas-Espitia S. , Marcial-Toledo S. , Guzman-Patraca C. , Perez-Romero J. , Saldana-Tellez M.
Published: August 2020

1521

Background: Breast cancer is the second cause of death from cancer among Mexican women but the incidence continues to rise mainly in rural communities. However, among women older than 50 years, only 7% of them report having had a mammogram because of insufficient number of mammography equipment and trained health care professionals. Mammography has limitation in sensitivity and specificity greater than 70 % and greater than 80 %, respectively. Breast thermography is a noncontact, noninvasive technique and easy to use outside hospitals. We propose to evaluate the feasibility of thermal infrared imaging as screening tool for early detection of breast cancer. Methods: Between November 2006 and December 2008, women were offered clinical breast examination (CBE) followed by breast thermography and mammography, and biopsy if indicated. Thermal infrared imaging was obtained by using an infrared camera (DL-700; 320*240 UFPA, Zhejiang Dali Technology Co., Ltd.). Infrared imaging was performed in a controlled environment with temperature and humidity maintained between 18 ºC and 23 ºC. Breast thermography diagnosis was established according to Hobbins criteria where TH1 to TH5 are equivalent to BI-RADS I to V (Intermer J of Rad 1987;12:337). CBE and breast thermography were correlated with mammography and histologic diagnosis. Results: Nine hundred and eleven (100%) women (median age 44 years, range 15–83) were evaluated. Five hundred and three (55%) of them were older than 40 years, 137 (15%) were between 35 and 39 years. Cancer was diagnosed in 14 (3%) and 2 (1.4%) women, respectively. Overall cancer was diagnosed in 16 (2.5 %) out of 640 women older 35 years. Among 116 (13%) women between 30 and 34 years, cancer was found in 1 (0.8 %) patient. Cancer was not found among 155 (17%) women between 15 and 29 years. Conclusions: In this study cancer was diagnosed in 1.8 % of women by using breast thermography. Thermal infrared imaging allows to select patients who could require further work-up. Breast thermography emerges as a potential screening tool for early detection of breast cancer.

No significant financial relationships to disclose.
Evaluation of the effect of screening on the detection of good and poor prognosis breast cancers
Authors: van 't Veer L. J. , Esserman L. J. , Linn S. , Rutgers E. , Knauer M. , Retel V. , Davis S. E. , Lin C.
Published: August 2020

1525

Background: Since the advent of screening, breast cancer incidence has significantly increased in the United States as well as other countries. SEER data from the US shows that the increase is largely in localized disease without a concomitant or significant decrease in regionalized disease. In addition, the increase has occurred essentially in women over 50. We asked whether molecular characterization of tumors would shed light on the types of tumors detected in screening and in locally advanced breast cancers (LABC). Methods: We identified two groups of patients from European studies before and after the introduction of population based screened (in 1995) where the 70-gene prognosis test (MammaPrint) results were available. The first source is the European Validation Study (EVS) (Buyse et al, J Natl Cancer Inst. 2006). The second was a prospective implementation trial of MammaPrint in the Netherlands (RASTER study) (Bueno de Mesquita et al, Lancet Oncol. 2007). The source of LABC patients comes from the multicenter I-SPY TRIAL (CALGB 150007/150012) who underwent routine screening (prior mammogram within 2 years of diagnosis). Results: In women age 50–60, the fraction of cancers that were MammaPrint good prognosis were 40% and 60% prior to and after the introduction of screening, respectively. For women 50–60 who were actually undergoing screening, the fraction of tumors that were MammaPrint good prognosis was 67%. For patients aged 30–40 with stage I and II lymph node-negative disease, who did not undergo screening in either period, the fraction of MammaPrint good prognosis tumors did not change (29% and 31%, for EVS and Raster, respectively). For patients with LABC, from the I-SPY TRIAL, the fraction of tumors that are MammaPrint good prognosis is 7% and 29% for women aged 30–40 and 50–60, respectively. Of the LABC patients undergoing screening, 80% presented clinically during the interval between routine mammograms. Conclusions: Current screening programs are increasing the burden of low-risk cancers. Screening programs should consider including molecular profiles at the time of diagnosis to reduce overtreatment. The majority of LABCs have high-risk molecular profiles and do not present as screen detected cancers. New strategies are needed for early detection of LABC.

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Delays in presentation and treatment of breast cancer in Nigeria
Authors: Ezeome R. E.
Published: August 2020

1527

Background: Programs on breast cancer prevention inresource poor countries often emphasize cost effective interventions to increase the uptake of screening, breast awareness, and the use of breast self examination. The success of such programs depends on the response of women and health professionals to the presence of symptoms of breast cancer. Understanding the factors at play in these responses is a prerequisite for strategies to shorten delays and improve stage at diagnosis. This study was designed to assess the delays and define the causes of delays in getting medical treatment by patients with breast cancer at University of Nigeria Teaching Hospital Enugu, (UNTH-E), Nigeria. Methods: A cross-sectional survey of consecutively presenting patients with breast cancer at the Surgical Oncology unit of the UNTH-E, Nigeria, was carried out between June 1999 and May 2005. A structured questionnaire was used to explore delays and the factors that influence delays in presentation and treatment of breast cancer. Results: One hundred and sixty four patients with breast cancer were interviewed. Most of them were married (71.2%), literate (84.7%), low (58.8%) or middle socioeconomic class (40%), and had access to hospitals within their area of residence. Most (81.6%) reported first for treatment at a modern health facility while 17.5% used alternative practitioners first. Twenty-six percent (42) presented within a month of noticing the symptoms while 45.3% (72) delayed for 3 months or more. In contrast, 17% (18) were seen at the site of definitive treatment within 1 month of seeking help at the initial hospital while 73.4% had a delay of more than 3 months after the initial hospital contact. Institutional or physician related delays were present in 44.5% of the cases while patient-related delays were present in 76.7% of cases. Only use of alternative practitioners as the first treatment point was significantly related to delays of more than 3 months before presentation (p = 0.029). Conclusions: For breast cancer prevention programs in Nigeria to succeed, they must, in addition to breast awareness and screening programs, address the institutional bottlenecks, the dearth of knowledge among primary care physicians, and improved referrals from alternative practitioners.

No significant financial relationships to disclose.
Influence of the dramatic fall of hormone replacement therapy (HRT) prescription on postmenopausal breast cancer incidence: The Austrian data
Authors: Pfeiler G. , Glatz C. , Königsberg R. , Vutuc C. , Kubista E. , Singer C.
Published: August 2020

1529

Background: The Women's Health Initiative trial showed a significant increase in breast cancer risk among women using HRT. This publication led to a dramatic fall in HRT prescription worldwide. Several studies argued that the ensuing decline in breast cancer incidence among postmenopausal women was due to the reduced HRT prescriptions. We have investigated whether the strong decline in HRT prescription in Austrian women from 2002 onward was associated with a decrease in postmenopausal breast cancer incidence in Austria. Methods: Breast cancer incidence data were obtained from the National Austrian Cancer Registry. HRT prescription data were calculated using Pharmaceutical Benefits Scheme data. Hormone receptor expression data were taken from the pathology report of all patients with breast cancer, who were operated on at the Division of Special Gynecology, as well as the Department of Surgery, Medical University of Vienna (MUW), from 1998 to 2000, and 2005 to 2007, respectively. Chi-Square test was used to identify significant differences. Results: HRT prescription slightly increased from 1998 to 2000, but dramatically decreased by 70% after 2003, reaching a significantly lower level. When comparing breast cancer incidence data from 1999 and 2004, a nonsignificant trend toward a decreased incidence in 50- to 54-year-old women could be observed. Comparing predicted breast cancer incidence for 2004 with the actual incidence for 2004 in this group, a significant decrease could be demonstrated. Ten percent to 12% of all new breast cancers in Austria are treated at the MUW every year. Regarding histopathologic breast cancer parameters of patients treated at the MUW from 1998 to 2000 and 2005 to 2007, respectively, a nonsignificant decline of hormone receptor positive tumors in 50- to 54-year-old patients with breast cancer could be observed. Conclusions: The decline of HRT use in Austria is associated with a reduction in breast cancer incidence in postmenopausal women. Our data underline the association between HRT and breast cancer.

No significant financial relationships to disclose.
Counseling and care: A Breast Cancer Awareness Training to improve participation and adherence to screening recommendations in women with a family history of breast cancer
Authors: Artmann A. , Gottschalk N. , Jacobs V. R. , Meindl A. , Kiechle M. , Rummeny E. J. , Harbeck N.
Published: August 2020

1530

Background: BRCA1 or BRCA2 mutation carriers are at an increased lifetime risk to develop breast and ovarian cancer. In a substantial number of families with affected members the known susceptibility genes cannot be identified. According to the recommendations of the German Consortium for Hereditary Breast and Ovarian Cancer, women with a hereditary predisposition for breast cancer should participate at an intensified surveillance program (ISP) including genetic counseling, risk estimation, BSE, CBE, BreastUS, MX, and MRI. Nonadherence might be influenced by cancer worryness, anxiety, health beliefs, and a lack of information about screening benefits.The aim of this investigation was to evaluate the impact of an indivualized Breast Cancer Awareness Training to improve the participation and adherence towards an ISP. Methods: Since 2005, an at-risk sample of 46 non-participating women (mean age 29 y; range 19–43 y) got an intensive breast cancer awareness training, including structured BSE, specific information about regular follow-up, screening advice, and radiological diagnostic procedures. To establish invidualized counseling and training particular needs (e.g., reasons for non-adherence, health beliefs and behaviours), risk perception, anxiety, and sociodemographic factors were evaluated by interviews and self-report questionnaires. The control group consisted of 38 participants of the ISP. Results: Breast cancer worry, anxiety, and lack of information about the benefits of screening programs were the main reasons for non-adherence. Within 3 months after the base counseling participation rates in MX (>30J), BUS, MRI, and CBE reached 98%. The numbers remain consistent in a 2-year follow up. 80% of participants practice BSE monthly, and 46% reported changes in lifestyle regarding nutrition, obesity, and health beliefs. Conclusions: Our approach emphasizes importance of self confidence and awareness for participation at the ISP for women at high breast cancer risk. Individualized counseling, BSE, re-evaluation, and reinforcement sessions are correlated with changes in health beliefs and behaviours for enhancing participation and adherence in women with a family history of breast cancer.

No significant financial relationships to disclose.
Ethnic/racial barriers to cervical cancer prevention with the HPV vaccine
Authors: Gorin S. , Westhoff C.
Published: August 2020

1546

Background: High risk types of the human papilloma virus (HPV) are necessary though not sufficient causes of the vast majority of cervical cancers. Black women have the highest prevalence of HPV (20.6%, 95% CI, 19.8–21.5%), followed by Latinas (14.1%, 95% CI, 13.9, 14.4%). Black women have the highest rates of mortality from cervical cancer, followed by Latinas. Recent population-based data reveal low uptake of the HPV vaccine (∼25%), particularly among Black women and Latinas. Objectives: The aim of this systematic review is to describe the supports and barriers to HPV vaccine inoculation among Black and Hispanic U.S. women. Methods: We conducted a systematic literature review of studies with more than one observation point or a comparison group that were published over the past 10 years, using a standardized extraction protocol. Inter-rater reliability rates were high (> 0.98). Of 64 English-language articles from peer-reviewed journals, we selected 16 for review. Results: We found barriers at the policy, provider, and patient levels. Barriers at the policy level include access to health care, cost, insurance coverage, vaccine availability, limited knowledge of the HPV vaccine, and media coverage that stigmatizes inoculation. At the provider level, knowledge about HPV incidence and transmission as well as physician recommendation are important factors that influence parental and patient acceptability of the HPV vaccine. Providers report difficulty in discussing STIs with parents, preadolescents, and adolescents. Providers are hesitant to store a vaccine that will be less widely used. Office-based procedures present structural impediments to dissemination of the vaccine. At the patient level, barriers include limited awareness of the vaccine, socioeconomic status, perception of risk based on sexual history, fear of vaccine safety, socio-cultural, economic, and religious factors. Conclusions: Policy, provider, and patient-focused intervention approaches to increasing dissemination of the HPV vaccine are proposed to increase uptake among Black women and Latinas.

No significant financial relationships to disclose.