bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of trastuzumab on the pathological complete response (pCR) rates in primary systemic therapy for breast cancer
Authors: Mizuta N. , Nakajima H. , Sakaguchi K. , Hachimine Y. , Fujiwara I.
Published: March 2020

11000

Background: Various regimens of primary systemic therapy (PST) have been performed to patients with locally advanced breast cancer to decrease the size of the primary tumor and allow for effective local and distant control. In terms of pathological complete response (pCR) rate, however, satisfactory results were not obtained. Therefore, in this study, we have tried to determine whether the addition of trastuzumab on PST could increase pCR rate. Methods: Two prospective nonrandomized studies were performed that used different regimens as PST, followed by breast conserving surgery. Group-A ; Eighty-fore HER2-negative patients with operable breast cancer were assigned to 4 cycles of epirubicin and cyclophosphamide followed by 12 cycles of weekly paclitaxel. GroupB; Eighteen HER2-positive patients were assigned to 4 cycles of epirubicin and cyclophosphamide followed by 12 cycles of weekly paclitaxel and trastuzumab. Results: A total of 102 assessable patients were enrolled, and all the patients have completed the above 2 regimens of PST. Pathological complete response (pCR) rates were 12% in Group-A and 61.1% in Group-B, respectively. Following the PST, 75% of Group-A and all of Group-B patients were able to be subjected to breast conserving surgery. All the toxicities happened in both groups were well controlled in grade 1 or 2. Conclusion: These results indicate that both the PST regimens were safely performed in women with locally advanced breast cancer and allow breast conserving surgery in a high fraction of patients (90%). In addition, significantly high rates of pCR were obtained in patients with use of trastuzumab (p<0.01).

No significant financial relationships to disclose.
Association between standard clinical and pathological breast cancer characteristics and the 21-gene recurrence score: A population-based study
Authors: Wolf I. , Ben-Baruch N. , Shapira-Frommer R. , Rizel S. , Goldberg H. , Yaal-Hahoshen N. , Klein B. , Geffen D. B. , Kaufman B.
Published: March 2020

11002

Background: The 21-gene recurrence score (RS) aims to quantify chemotherapy benefit in lymph node-negative, estrogen receptor (ER)-positive breast cancer (BC) patients. We aimed to elucidate the association between the RS and clinical-pathological features in a population-based Israeli cohort. Methods: Study population included all Israeli BC female patients referred to the RS assay from October 2004 until October 2006. Clinical and pathology data were collected upon referral, RS risk was categorized as previously defined (low < 18, intermediate 18–30, high = 31) and chemotherapy benefit was also assessed for each patient using NCCN guidelines, St. Gallen recommendations and Adjuvant! Online. Results: 300 patients were referred to the assay by 70 physicians from 16 institutions. Low, intermediate and high RS were noted in 109 (36 %), 134 (45 %) and 57 (19%) of the patients respectively, compared to 54%, 21% and 25% respectively, in the validation study (JCO;24:3726). Median age was 54 and median tumor size was 1.6 cm. Similar age distribution, tumor size and ER staining intensity were noted in all risk categories. Interestingly, no association has been identified between the RS and the presence of lymph nodes micrometastases. High tumor grade was noted in 15%, 20% and 56%; progesterone expression in 88% 72% 43%; non-infiltrative ductal carcinoma (IDC) 24%, 12% and 6%; and Her2 expression in 2%, 3% and 19% of the low, intermediate and high risk categories respectively (p<0.0001 for all variables). Risk assessment according to clinical guidelines or Adjuvant! Online correlated poorly with the RS. Conclusions: Risk stratification of referred Israeli patients differs from that of the validation study population. Moreover, the RS did not correlate with age, tumor size and ER intensity. The RS correlated with histology, grade, PR and Her2 expression and may be predicted, in specific subsets of patients, using these features. However, RS categorization cannot be predicted by commonly-used clinical predicting tools.

No significant financial relationships to disclose.
Analysis of the prognostic value of the shed antigen of HER2/neu in premenopausal breast cancer patiens in the TABLE study
Authors: Luftner D. , Pechlivanis K. , Geppert R. , Stroux A. , Possinger K.
Published: March 2020

11007

Background: The HER-2/neu oncoprotein is a transmembrane tyrosine kinase that belongs to the family of epidermal growth factor receptors. It is known to be overexpressed in 20–40% of breast cancers. Increased serum HER-2/neu (sHER-2/neu) concentrations at the beginning of adjuvant breast cancer therapy have been shown to be of prognostic importance (Mehta et al, 1998). Using the sera from the Takeda® Adjuvant Breast Cancer Study with Leuprorelin (TABLE study), we tested for the prognostic value of sHER-2/neu. Methods: A total of 133 premenopausal, node-positive, hormone-receptor positive patients received either 11.25 mg of leuprorelin s.c. every 3 months over 2 years or CMF chemotherapy for 6 cycles. Blood samples were collected at baseline and at 3, 6, 12, 18, 24 and 30 mo. The primary endpoint of the study was to determine the relapse-free survival (RFS) after 2 years. sHER-2/neu was measured using a standardized ELISA (upper limit of normal 15 ng/ml). As the baseline sHER-2/neu concentrations ranged from 3.8–14.0 ng/ml, results were grouped in terciles. Data were analyzed using Kaplan-Meier and Cox Proportional Hazards survival analysis. Results: Material was available from 80 patients in leuprorelin arm and 53 patients in CMF arm. 65 of 133 patients had relapsed during the follow-up time of up 7 years after treatment. The median RFS was 62.9 mo. The RFS time depended on the concentrations of sHER-2/neu at baseline: RFS was significantly shorter in patients of the third tercile with sHER-2/neu levels >8.8 ng/ml than in patients of the first tercile with levels <7.2 ng/ml (p=0.0232). Five years after initial therapy, we found that 73% of patients in the first tercile group of baseline sHER-2/neu had no relapse. In the second tercile, 63.3% of patients were relapse-free, while in the third tercile only 47.2% of patients had not suffered from a relapse. Conclusions: Higher sHER-2/neu concentrations at the beginning of adjuvant therapy in the TABLE-Study have a prognostic importance for RFS. This observation was evaluated irrespective of the HER-2/neu tissue status and could be of clinically importance for adjuvant therapy with the monoclonal anti-HER-2/neu antibody trastuzumab or other anti-HER-2/neu targeted therapies.

No significant financial relationships to disclose.
Outcomes in double-negative (HER2/PR negative) LABC phenotype treated with cisplatin-based primary chemotherapy: Impact of intensified regimen
Authors: Ionta M. T. , Atzori F. , Deidda M. C. , Murgia M. , Frau B. , Coinu A. , Barca M. , Eltrudis F. , Minerba L. , Massidda B.
Published: March 2020

11024

Background: It is widely assumed that HER2-negative and hormone receptors negative tumors (Triple-Negative as TN) are associated with poor outcome and would benefit from intensified chemotherapy and/or from specific EGFR-targeted therapies.Nevertheless, the lack of PR expression in presence of ER-pos tumors, (Double-Negative as DN) could reflect an aberrant growth factor signaling, identifying a more aggressive phenotype than ER-pos/PR-pos tumors that could contribute to the tamoxifen resistance and that could benefit from tailored specific treatment such as TN pts. Aim of our retrospective study was to evaluate,the clinical outcome among a group of LABC pts, according to the treatment’s schedule (standard vs intensified) and TN or DN phenotype. Methods: Between June 1996 and November 2001, 72 consecutive LABC pts, (77 % T4abc; 23 % T4d) median age 51 (29–70), ER/PR-neg 37,5%; ERpos/PR-neg 33%, were treated with primary PEV regimen (cisplatin 50 mg/m2; epirubicin 100 mg/m2; vinorelbine 25 mg/m2):q 3wks x 4 cycles in the first 24 pts (Standard); q 2 wks x 6 cycles in the subsequent 48 pts (Intensified), followed by adjuvant RT,CMF and TAM ± LH-RH ; 50 pts of 72 were IHC assessable for both HER2 and HR: 39 pts (78%) were identified as HER2-neg; 25 (64%) of 39 were HER2-neg/PR-neg irrespective of ER status, (any ER), of whom 12 were ER-neg (TN )and 13 were ER-pos ( DN ). Results: At a median follow up of 88 months (58–123) DFS was 20% and 80%; 20% and 100%; 20% and 62,5% in standard group and in intensified group respectively; OS was 40% and 80%; 40% and 100%; 40% and 62,5% in standard group and in intensified group respectively. Conclusions: Our findings suggest that DN as well as TN pts benefit from intensified primary chemotherapy. Therefore, tailored treatments are warranted for DN as well as TN pts. In addition, our data indicate that association of HER2-neg with PR-neg independently of ER expression (any ER) could be correlated with a more aggressive phenotype.

[Table: see text]

No significant financial relationships to disclose.
Impact of the ATAC trial on prescribing of hormonal therapy in breast cancer
Authors: Connolly R. M. , Barron T. I. , Bennett K. , Feely J. , Kennedy M. J.
Published: March 2020

11028

Background: The arimidex, tamoxifen, alone or in combination (ATAC) trial recommended use of anastrazole over tamoxifen as initial adjuvant hormonal therapy of early breast cancer in postmenopausal women. The aim of this study was to investigate the impact of the publication of the ATAC trial in December 2004 on subsequent prescribing of hormonal therapy to Irish women =55 years old. Methods: The Irish HSE-PCRS pharmacy claims database was used to identify all women =55 years old, commenced on tamoxifen or an aromatase inhibitor as initial hormonal therapy, between July 2000 and June 2006. A segmented regression analysis of an interrupted time series was used to detect changes in the trend and level of anastrazole prescribing after publication of the ATAC trial in December 2004 and the prior updates in November 2003 and June 2002 (presented December 2001). β coefficients and 95%CI are presented where appropriate. The absolute change in anastrazole prescribing and 95%CI are also calculated for selected months. Statistical analysis was performed using SAS version 9.1. Significance at p<0.05 is assumed. Results: A cohort of 7,604 women =55 years old, commenced on initial hormonal therapy, was identified from the HSE-PCRS database, 2,206 (29%) of these women were prescribed anastrazole. In the month following publication of the final results of the ATAC trial there was a 17.6% (95% CI 10.8%, 24.5%) absolute increase in anastrazole prescribing. This represented a statistically significant increase in the level of prescribing (level change β=18.1 95% CI 11.3, 24.9 p<0.0001). There was also a significant change in anastrazole prescribing trend after presentation of the first ATAC update (slope change β=0.98 95% CI 0.59, 1.37 p<0.0001). Conclusion: The publication of the final ATAC trial data resulted in a significant increase in the prescribing of anastrazole. This is objective evidence that oncologists respond rapidly to clinical trial results. It is unclear whether the significant increase in anastrazole prescribing after the first ATAC update is an appropriate response to an interim analysis.

No significant financial relationships to disclose.
Phase I/II study of a 3 weekly liposome-encapsulated doxorubicin/docetaxel/pegfligrastrim in combination with weekly trastuzumab as primary treatment in HER2 positive (HER2+) early stage breast cancer (ESBC) patients (pt). GEICAM 2003–03 study
Authors: Antón A. , Ruiz A. , Seguí M. A. , Calvo L. , Muñoz M. , Lao J. , Vázquez C. , Fernández L.
Published: March 2020

11032

Background: The liposome-encapsulated form of doxorubicin (Myocet™) (M) seems to be safe in terms of cardiotoxicity in combination with standard doses of trastuzumab (H) and paclitaxel in BC. This phase I/II study of M, H, docetaxel (T) and pegfligrastrim (N) was designed to evaluate the efficacy and safety of the combination, and define the MTD, in order to examine the selected regimen in a phase II trial. Methods: Cohorts of 3 HER2+ (FISH+) ESBC pt were treated at fixed dose of N (6 mg) and H (2 mg/kg/week). M and T were administered at the following dose levels (DL) (mg/m2): DL0, 60/75; DL-1, 55/75; DL-2, 50/70; DL-3, 50/65; DL-4, 50/60. The MTD was defined as >1/6 pt in any cohort experiencing a predefined dose-limiting toxicity (DLT) in cycle (cy) 1 or 2. LVEF was assessed at baseline and every 2 cy. Results: Nineteen pt have been enrolled in phase I; all are evaluable for efficacy and toxicity. Median age was 45. Twelve pt (63%) were premenopausal. Median tumour size was 45 mm (20–80); 13 (68%) and 6 pt (32%) presented with stage II and IIIA BC respectively. Six (32%) of tumours were G3. DLT were G3 diarrhoea, febrile neutropenia, thrombocytopenia, infection, and G4 asthenia. Three additional pt were treated at DL-4 for confirmation of the recommended dose; none of them had a DLT. One pt (DL-2) experienced asymptomatic, reversible LVEF decrease to 49%. All pt have been assessed for pathological response: 6 (32%) and 5 pt (26%) achieved one pCR and one pPR in breast, defined as Miller and Payne score of 5 and 4, respectively. Conclusions: Concomitant administration of M plus THN is highly active regimen with manageable toxicity in pt with HER2+ ESBC tumours. DL-4 has been selected as the DL for the ongoing phase II study with an enrolment target of 59 pt.

No significant financial relationships to disclose.
Randomized comparison of neoadjuvant docetaxel (D), epirubicin (E) and pegfilgrastim (P) (+ trastuzumab [T] in HER2+ patients [pts]) with and without capecitabine (C) for operable breast cancer (BC): Results of a planned safety analysis of ABCSG 24
Authors: Steger G. G. , Greil R. , Samonigg H. , Jakesz R. , Bartsch R. , Mlineritsch B. , Melbinger-Zeinitzer E. , Marth C. , Schippinger W. , Gnant M. F.
Published: March 2020

11034

Background: ABCSG-24 is assessing the effect of adding C to DE and adding T to DE or DEC on pCR rate. Methods: Pts with operable BC (any T stage except T4d, N±, M0) scheduled for pre-operative chemotherapy were randomized to six 3- weekly cycles of D 75 mg/m2, d1 + E 75 mg/m2 d1 + P 6 mg d2, ± C 1,000 mg/m2 bid d1–14. Primary endpoint was pCR rate. After protocol amendment, HER2+ pts were also randomized to adjuvant ± neoadjuvant T. Results: From Nov 04 to Nov 06, 262 pts were enrolled, including 29 HER2+ pts. 145 are evaluable (DE: 74 pts, 400 cycles; DEC: 74 pts, 344 cycles). The table shows grade 3/4 adverse events (AEs) in >2% of pts in either arm. Febrile neutropenia was absent. Serious AEs occurred in 22% vs 20% of pts in DE vs DEC, respectively. Fewer pts in the DE than the DEC arm required dose reduction (0.5% vs 6.6% of cycles), withdrew consent (4% vs 13%) or were withdrawn by the investigator (1% vs 17%). Reasons for withdrawal by investigator were: HFS, stomatitis, mucositis, diarrhea, vomiting, peripheral neuropathy, fatigue, asthenia, docetaxel hypersensitivity, and asymptomatic liver enzyme elevation. No serious or grade 3/4 cardiac toxicity has occurred with T. Conclusions: Despite infrequent grade 3/4 AEs in both arms, more pts discontinued DEC than DE, by either patient’s or investigator’s choice. Since May 06, no DEC pts have withdrawn consent, perhaps because of improved pt education and symptom management. This finding reinforces the need for close monitoring and prompt management of AEs. The addition of C to DE presents no safety concerns. Efficacy results are due in 2008.

[Table: see text]

[Table: see text]
Bone mineral density in women with non-metastatic breast cancer: Effect of intravenous bisphosphonates given before adjuvant therapies
Authors: Alonso B. , Aleman R. , Rodríguez L. , Llanos M. , Cruz J. , Oramas J. , Rodríguez E. , García R. , Ponce S. , Batista J.
Published: March 2020

11038

Background: Adjuvant therapies shown survival improve of non-metastatic breast cancer (NMBC) patients, but they also decrease bone mineral density (BMD). Bisphosphonates are effective agents for the management of osteoporosis. Intravenous zoledronate, which is approved for the treatment of malignant hypercalcemia, multiple myeloma, and skeletal metastases, can suppress bone resorption and are often considered first-line therapy for the treatment of osteoporosis. We have analyzed the effects of chemotherapy on BMD of women with NMBC who received before adjuvant therapies intravenous bisphosphonates (zoledronic acid). Methods: We prospectively studied the effects of a single intravenous zoledronic acid dose (4 mg), on BMD of 74 women with NMBC (stage I-III), administred previous to the adjuvant therapies. The patients were referred to the Medical Oncology Service of University Hospital of Canary Islands between 2003 y 2006. Lumbar and hip BMD (g/cm2) was measured at diagnosis and after chemotherapy. The results were compared with a group of 80 patients with NMBC who received adjuvant therapy without intravenous bisphosphonates. Results: Breast cancer patients the median age was 52 ± 10 years old and the body mass index was 28,2 ± 5.5 kg/m2. At baseline there were not differences in BMD between the group that received bisphosphonates and the group with only chemotherapy at any of lumbar or femoral bone sites. In our study, the BMD after chemotherapy and intravenous bisphosphonates (n=74) significantly increased at femoral neck (0.805 ± 0.01, 0,826± 0.12; p=0.002) and trochanter (0.709 ± 0.01, 0.724 ± 0.01; p=0.002) and remained stable at lumbar, intertrochanter, total hip and Ward’s triangle; whether the group without bisphosphonates significantly decreased at lumbar (1.014 ± 0; 0.995 ± 0, p=0.0001), trochanter (0.701± 0; 0.690 ± 0, p=0,046), intertrochanter (1,095 ± 0; 1.078 ± 0, p=0.0001) and total hip (0,924 ± 0; 0.915 ± 0, p=0.046) areas (table). Conclusions: Women with NMBC are affected by early bone loss after adjuvant chemotherapy. Bisphosphonates intravenous (zoledronic acid) given before adjuvant therapy might be an effective treatment for this bone loss, increasing BMD or remaining stable.

No significant financial relationships to disclose.
Adjuvant hormonal therapy (AHT) in women with early stage breast cancer (BC).
Authors: Song X. , Nicholas G. , Dent S. , Verma S.
Published: March 2020

11053

Background: The ASCO technology assessment on adjuvant use of AI states that optimal AHT for a postmenopausal woman with HR-positive BC should now include an AI. We assessed uptake and patterns of AHT use in early stage HR-positive BC at a regional cancer center. Methods: A retrospective review of patients diagnosed with HR-positive early stage BC from January 2004 to December 2005 treated at our center was performed. Data included patient demographics, dates of diagnosis, treatment, last follow-up, AHT choices considered, patient compliance, and treatment toxicity. Patient risks for disease recurrence and mortality were estimated using adjuvantonline. Factors predicting a preference for AI use were identified using univariable and multivariable analysis. Results: 900 patients were identified for the stated period of time with HR-positive early stage BC. 340 patients have been evaluated. Median age was 59 years. Menopausal status was post-/ pre- in 267/73 patients. Stage was I/IIA/IIB in 202/95/43 patients. 267 patients were lymph node (LN) negative. ER, PR and Her2/neu status were positive/negative/unknown in 332/7/1, 292/46/2 and 11/69/260 patients. Initial AHT choice was tamoxifen/anastrozole/letrozole/exemastane/none in 196/79/9/2/54 patients. Of those started upfront on tamoxifen, plan to switch to an AI was stated in 41%. Statistically significant factors associated with any adjuvant AI use included disease stage, menopausal status as well as individual physician preferences. In further analysis, patients’ compliance and toxicity will be reported. Correlation of recurrence risk, as determined through adjuvantonline, with upfront selection of an AI has also been performed. Conclusion: Guidelines have stated the use of an AI (upfront, sequential or extended) should be considered in HR-positive early stage BC. Results from this study provide further insights on the uptake of such therapy as well as factors (disease related, patient and physician preferences) influencing adjuvant treatment decision-making. A prospective trial assessing treatment decision regarding AHT is also in progress. (This study is sponsored by the Canadian Breast Cancer Foundation)

No significant financial relationships to disclose.
Temporal trends in protocol-specified adjuvant chemotherapy dosing in obese patients with breast cancer
Authors: Greenman C. , Griggs J. J.
Published: March 2020

11055

Purpose: Dosing of breast cancer adjuvant chemotherapy in obese women varies substantially, with up to 40% of obese women receiving reduced (compared to full weight-based) doses. Such variation indicates uncertainty about best practices. This study reports changes over time in protocol-specified dose determinations in heavy patients. Methods: The National Cancer Institute database of cooperative group trials was used to identify completed clinical trials of non-myeloablative breast cancer adjuvant chemotherapy. Dose determinations specified in each protocol were categorized into one of four groups: 1) full weight-based dosing, 2) dose reduction in heavy patients (ideal or corrected body weight used to calculate body surface area, BSA), 3) dosing in heavy patients left to physician’s discretion, or 4) no specific instructions. Results: Of 110 eligible clinical trial protocols identified, 61 (55%) were retrieved. Of the 16 protocols initiated before 1985, 15 (94%) either did not address dose determination (n = 6) or specified dose reduction (n = 9) in heavy patients. Of the 45 protocols initiated after 1985, 26 (58%) specified full weight-based dosing, 13 (29%) specified dose reductions, 4 (9%) left dosing in heavy women to the physician’s discretion, and 3 (7%) had no specific instructions for dose determinations in heavy patients. The difference in the use of full weight based doses before and after 1985 was statistically significant (p value = 0.0003, 2-sided Fisher’s exact test). One of the cooperative groups, which contributed 10 of the 45 (22%) clinical trial protocols since 1985, specifies a maximum BSA of 2.0 m2 for cyclophosphamide and doxorubicin in all protocols. Conclusions: Over the last two decades, dose determinations in clinical trial protocols have, with the exception of one cooperative group, specified use of actual body weight. Present-day dose reductions in obese patients who are not participating in clinical trials suggest a lack of diffusion of information about optimal dosing in obesity. The continued practice of limiting the doses of cyclophosphamide and doxorubicin in patients with a BSA over 2.0 m2 in the protocols of one cooperative group may contribute to persistent uncertainty about optimal dosing in heavy patients.

No significant financial relationships to disclose.
Breast cancer after treatment of Hodgkin disease: Clinical outcome of 38 cases in 27 patients
Authors: Alm El-Din M. A. , Hughes K. S. , Goldberg S. I. , Raad R. A. , Taghian A. G.
Published: March 2020

11059

Background: Many studies showed that women who are cured of HD have an increased risk of developing BC. Our purpose is to evaluate detection, pathology, management and prognosis of BC occurring after HD. Methods: Thirty-eight cases of BC in 27 survivors of HD were analyzed. All patients received supradiaphragmatic RT and 13 had also chemotherapy for HD. Results: The median age of the patients at diagnosis of HD was 25.5 years. The median interval to develop BC was 15.9 years. The median age at diagnosis of BC was 45.8 years. Ten women (37%) had bilateral disease; one of them had DCIS, 7 years before developing bilateral disease. Cancers were detected by mammography (59.4%), symptom presentation (24.3%), clinical examination (8%), and incidental during elective mastectomy (8%). Using Fisher’s Exact test, DCIS was more frequent (27%), where nodal involvement (29.6%), and ER positivity (81.5%) were paralleled that reported in general population. Thirty tumors (79%) were managed by mastectomy due to prior RT. Two women received RT following mastectomy. Eight tumors treated by lumpectomy, followed by RT in two women; one received whole breast RT, while the other received fractionated partial breast irradiation using 3D-conformal technique (50Gy/25 fractions) and she is doing well 1 1/2 years after RT. Adjuvant systemic therapy, given to 17 patients, was well tolerated. The median follow-up after BC was 61 months. Using Kaplan-Maier procedure, the 6-year actuarial relapse-free survival for node-negative BC after HD was 100%. Node positive patients had a significantly lower RFS of 58.3% ± 19% (P = 0.01). Conclusions: Compared to patients with primary BC, patients developing BC after HD are more likely to be younger, have bilateral disease and have more frequent DCIS. Other pathological features and prognosis are similar to that reported in general population. Patient awareness, breast examination and mammography should be part of the follow-up program for HD survivors. Mastectomy remains the standard of care in most of cases; however, lumpectomy followed by fractionated partial breast irradiation might be a reasonable approach to investigate for women who refuse mastectomy.

No significant financial relationships to disclose.
Use of oblique supine magnetic resonance imaging in breast-conserving surgery following neoadjuvant chemotherapy
Authors: Nakamura R. , Sakakibara M. , Nagashima T. , Fujimoto H. , Arai M. , Hashimoto H. , Kaneoya K. , Ueda T. , Miyazaki M.
Published: March 2020

11064

Background: The success of breast-conserving surgery (BCS) after neoadjuvant chemotherapy (NAC) is dependent on accurate assessment of the extent of surgical excision of the original tumor bed (OTB). However the difficulty in locating microscopic residual disease often leads to a high re-excision rate (RER) and large excision specimen area (ESA). Methods: Magnetic resonance imaging (MRI) scans in the oblique supine position are performed with the patient in the same posture as that adopted during surgery. Maximum intensity projection (MIP) images of MR coronary section images of OTB are generated and used for surgery. OTB images are copied onto transparent sheets overlaid on the MIP images. These images are projected onto the breast before surgery, and used to determine the lines for surgical excision. In the conventional method (CM), OTB is determined by ultrasonography (US) and CT images. The oblique supine MRI method (SMM) has been used at our hospital since 2005. In this study, 14 patients treated prospectively with SMM (12/05- 12/06) were compared with a series of 19 consecutive patients treated with CM (04/03–11/05). ESA and RER were analyzed. Re-excision was performed in cases with a calcified lesion or tumor within 1 cm of the excised margin by X-ray or US during surgery, or invasive cancer was detected within 1 mm by pathological examination. ESA was analyzed using NIH Image. All patients received anthracycline/taxane-based chemotherapy. Results: There were no significant differences in characteristics of patients in the initial stages (T1, 2) or pathological chemotherapy responses between SMM and CM groups. There were four T3.4 cases in the SMM group, but none in the CM group. Clinical responses in CM and SMM were as follows (cases): CR 6, 7; PR 12, 7; SD 1, 0, respectively. RER was significantly greater in CM (36.8%, n=7) than in SMM (7.1%, n=1) (P<0.05). Average ESA in SMM were 19.0 cm2 (n=2) in T1, 33.6 cm2 (7) in T2, and 59.3 cm2 (5) in T3.4, while corresponding values in CM were 49.4 cm2 (4) and 65.5 cm2 (15), respectively; ESA was significantly improved in SMM. Conclusions: SMM, which has the benefits of decreased ESA and RER with superior cosmetic results, is a reliable technique for BCS following NAC.

No significant financial relationships to disclose.
The effect of aromatase inhibitors on bone mineral density measured by serial DXA scans
Authors: Whannel K. J. , Doughty J. C. , Wilson C. R. , McLellan A.
Published: March 2020

11065

Background: We are now using aromatase inhibitors (AI) in increasing numbers of women as treatment in the breast cancer care pathway. Studies have reported a loss of bone mineral density (BMD) with use of all AIs. It has been shown in our unit that 5 years of tamoxifen (T) in post-menopausal women prior to commencing an AI does not offer sufficient protection to prevent significant BMD loss when an AI is introduced, with 25% requiring concurrent bisphosphonate (BP) therapy. The aim of this study was to determine changes in serial DXA scan results over a 12month period in women taking AIs. Method: 62 women being considered for or in early stages of use of an AI attended for a DXA scan and re-scan at 12 months. Vertebral morphometry and fracture rate were assessed and risk factors for osteoporosis noted. Scan results were compared ( Table 1 ). Results: Mean age was 67yrs [standard deviation (SD) 9yrs]. The patients were grouped according to initial endocrine therapy. 13 (21%) switched from tamoxifen to arimidex after 2years, 3 (4.8%) switched from tamoxifen to exemestane after 3 years and 30 (48.4%) switched from tamoxifen to letrozole after 5 years. 11 (17.7%) had been on arimidex as first line endocrine therapy for <=2 years and 5 (8.1%) had been on letrozole as first line endocrine therapy for <=1 year. Mean t-score and SD was calculated at each site and results categorised by lowest t-score at any site. The overall decrease in BMD measured at 1.66% over the 12 months. Conclusion: We have demonstrated a decrease in BMD with AI treatment of 1.66% per year as well as an increase in fracture incidence and increased need for bisphosphonate therapy whilst on an AI. We would recommend that all patients on any AI receive annual DXA scans. [Table: see text]

No significant financial relationships to disclose.
Utilization of oncotype DX in node-negative, ER-positive breast cancer patients
Authors: Patel H. , Hook K. , Kaplan C. , Davidson R. , DeMichele A. , Fox K. R. , Domchek S. M.
Published: March 2020

11067

Background: The 21 gene RT-PCR assay Oncotype DX (Genomic Health, CA) stratifies patients into low, intermediate and high risk for systemic recurrence. The objective of this study was to examine the patterns of use of Oncotype DX in a single institution. Methods: All patients who had ODX testing requested by the University of Pennsylvania were identified and recurrence scores (RS) obtained. Patient and tumor characteristics, as well as treatment administered, were obtained by chart review for analysis. Results: 100 ODX tests were ordered between 1/1/05–11/30/06. RS results classified 51% of breast cancers as low risk, 38% intermediate risk, and 11% high risk. Characteristics of the tumors of the overall population and by RS group are shown in Table . 99% of patients received hormonal therapy. Of the low risk patients, only one patient was treated with chemotherapy (2%) while 34% of the intermediate risk group and 80% of the high risk group received chemotherapy. Notably, only 4/100 patients with ODX were under age 35 and 17/100 had tumors over 2cm. Conclusions: In this series, ODX use is accelerating. The results of the ODX tests appear to be used clinically as demonstrated by the very low use of chemotherapy in the low risk group. Comparison to the overall population of ER positive, node negative patients seen at this institution is underway.

[Table: see text]

No significant financial relationships to disclose.
A phase II study of dose-dense chemotherapy (doxorubicin (A), cyclophosphamide (C), paclitaxel (T), gemcitabine (G)) supported by pegfilgrastim (P) and darbepoetin-alfa (D) for patients with high-risk early stage breast cancer (ICANDO)
Authors: Mainwaring P. N. , Shannon C.
Published: March 2020

11068

Background: The primary objective of this study was to estimate the proportion of chemotherapy dose delays in a dose- dense regimen consisting of A (60mg/m2), C (600 mg/m2) x 4 cycles q2 weeks followed by T (175 mg/m2) G (1g/m2) x 4 cycles q2w with pegfilgrastim (6 mg/m2 sc d2) and darbepoetin-alfa (2.25 microg/kg if Hb < 110g/L) as treatment for patients with high-risk early stage breast cancer. Dose delay was defined by the proportion of subjects experiencing delay = 7 days in any cycle. Entry criteria path stage IIA-IIIA breast adenocarcinoma; node positive patients > 6 axillary lymph nodes removed or sentinel LN biopsy positive for metastasis. Treatment commenced within 8 weeks. Secondary endpoints included proportion of delays by cycle, causes of delay by cycle, causes of dose reduction by cycle, as well as time to haematological engraftment. Patients underwent weekly FBC, electrolytes, LFTs, with a normal baseline echo assessment. Herceptin therapy was approved in Australia 1st October 2006 and was added to TG therapy for FISH/CISH/IHC 3+ positive patients. All patients completed FACT-F QOL forms. The half-width confidence interval to predict for delay based on the AC-T data is 0.17 for n = 20 patients. Results: Twenty (20) women; median age 50 (41–66) met the criteria for treatment. No patients had treatment delays ≥ 2 days for any reason. One (5%) patient underwent a blood transfusion for a rapid decline in haemoglobin (Hb) prior to darbepoetin therapy. One (5%) patient was admitted for uncontrolled vomiting. Seven (35%) patients received darbepoetin therapy without secondary Hb rise above 130 g/L. One (5%) patient had a 20% dose reduction in A dose due to mucositis. For nausea >G1 aprepitant therapy was added. There have been no dose modifications due to hepatic toxicity. Final cycle, QOL and pharmacogenomic data will be presented at the meeting. [Table: see text]

No significant financial relationships to disclose.
Predicting axillary lymph node involvement in breast cancer patients by ultrasonography
Authors: Rokutanda N. , Horiguchi J. , Koibuchi Y. , Nagaoka R. , Iino Y. , Takeyoshi I.
Published: March 2020

11075

Background: About 20% of breast cancer patients eligible for sentinel node (SN) biopsy have axillary node metastases. The purpose of this study is to evaluate the sensitivity of preoperative ultrasonography (US) for SN involvement. Methods: Between October 2004 and May 2006, a total of 141 breast cancer patients without clinically node involvement were eligible for SN biopsy. The size (length and height) and cortical thickness of lymph nodes (LN) was measured by US before surgery. Results: Twenty-four (20%) of 141 patients had pathologically involved LN (Positive Group), and 118 (80%) were negative for LN metastases (Negative Group). No LN was detected in 25 patients (21%) of the negative group by US. The number of detected LN was more in the positive group than the negative group (1.59 vs 1.13, p<0.05). There was no significant difference in the size of LN between the two groups. The cortical layer of LN was thicker in the positive group than the negative group (3.11 vs 2.12, p<0.05). Eighteen patients had the LN with more than 4mm of cortical thickness, nine (50%) of which revealed pathologically LN involvement. Conclusions: The measuring of cortical thickness is useful for predicting axillary LN involvement by US. This approach may improve the selection of patients for SN biopsy.

No significant financial relationships to disclose.
Locoregional control significantly reduces the risk of subsequent distant metastases in patients with locally advanced breast cancer managed with radiotherapy as the primary locoregional treatment
Authors: Rogowski W. , Badzio A. , Dziadziuszko R. , Madrzak J. , Welnicka-Jaskiewicz M. , Jassem J. , Barrett-Lee P.
Published: March 2020

11076

Background: The treatment results of patients with locally advanced breast cancer still remain far from satisfactory. Both lack of locoregional control and distant metastases remain the most common pattern of failuire. The aim of this study was to evaluate whether achieving locoregional control decreases the subsequent risk of distant metastases a large series of consecutive locally advanced breast cancer patients managed with radiotherapy as the primary locoregional treatment. Methods: The records of 261 primarily inoperable locally advanced breast cancer patients treated between 1991 and 1997 at two institutions: Medical University of Gdansk, Poland and Velindre NHS Trust, Cardiff, UK were analysed. All patients received megavoltage radiotherapy to the breast with two tangential fields, and the adjacent lymph node areas were irradiated using customised fields. In 241 patients radiotherapy constituted the only local treatment and the remaining 20 patients were subsequently subjected to mastectomy. Most patients received chemotherapy and/or endocrine therapy prior or after radiation therapy. Results: Follow-up ranged from 6 to 133 months (median 37 months). Five- year overall survival was 36% (95%CI: 28–43%) and 5-year loco-regional relapse-free survival was 48% (95%CI: 40–57%). Recurrence occurred in 167 patients (67%), including local recurence in 30 patients (12%), distant metastases - in 72 patients (27%) and both distant and local recurrence - in 65 patients (26%). Median time to distant metastases was significantly shorter among a subgroup of patients who presented locoregional failuire - 33 months as compared to patients who were free of locoregional recurrence or progression before presenting distant metastases-43 months (p<0.05) Conclusions: This study demonstrated that treatment results in patients with locally advanced breast cancer are still far from satisfactory. However it confirmed the importance of putting much effort in achieving locoregional control in that group of patients as it significantly reduces the risk of subsequent distant metastases.

No significant financial relationships to disclose.
Vitamin D (vD) deficiency (def) in breast cancer (BC) patients (pts)
Authors: Presant C. A. , Bosserman L.
Published: March 2020

11082

Background: Vitamin D metabolism is important for maintaining bone health and perhaps cancer prevention. Prior studies have reported vD def in 88% of brca pts (Lonning et al ASCO 2006 abst 554), and 79% of women (Chlebowski et al ASCO 2006 abst 6) . Methods: In order to determine the frequency of vD def, we studied 41 consecutive brca pts. Levels of vD were correlated with clinical features. Pts were classified as vD def if 25OH D <20, 1.25 diOH D <14, or D3 <20. Insufficiency (ins) of vD was 25OH D 20–29. Results: 8 pts had vD def (19.5%). This was more common in young pts <60 (37.5%) compared to older pts (8%) (p4) in 5/6 pts <60 and 5/7 older pts. vD def did not correlate with bone disease: 25% def in pts without bone disease, 17% in pts with osteopenia, and 17% in pts with osteoporosis. In older pts, vD was normal in 12/14 pts on anastrazole, and in 7/11 pts not on anastrazole, indicating no relation of anastrazole to vD def. Bisphosphonate (bis) usage was slightly higher in older pts (60%) versus younger pts (38%) but not significantly (p<0.2). While only 19% of pts on bis had vD ins or def, 50% of pts not on bis had ins or def vD (p<0.05). Although only 5% of pts on bis had vD def, 30% of pts not taking bis had vD def (p<0.05). Conclusions: In brca pts, vD def is less than reported, but still frequent. All brca pts should be tested for vD periodically. VD def may be less frequent in pts on bis, and confirmatory trials should be performed. VD levels should also be monitored even if pts report taking vD. VD def or ins should be treated and monitored by oncologists. Since vD may be related to cancer incidence, and to bone disease, all brca trials collecting data on bone events, bone density, and second cancers should also report relationship to vD levels in individual study participants.

No significant financial relationships to disclose.
Dose scheduling and pharmacokinetic (PK) study of trastuzumab in patients (pts) with HER2/neu overexpressing breast cancer?
Authors: Felici A. , Segni S. Di , Contestabile M. , Nuvoli B. , Fabi A. , Papaldo P. , Ferretti G. , Sperduti I. , Citro G. , Cognetti F.
Published: March 2020

1109

Has been demonstrated that 10–20 μg/mL is the minimum serum trough concentration (Cmin) of trastuzumab that causes maximal tumor growth inhibition. This concentration was shown to be achievable using a weekly (4 mg/kg loading dose followed by 2 mg/kg weekly) and a three-weekly (8 mg/kg loading dose followed by 6 mg/kg) schedule, but only indirect comparisons of the two schedule have been performed. We prospectively analysed the PK distribution of trastuzumab in three different schedules, as follows: weekly (cohort I), bi-weekly (trastuzumab 6 mg/kg loading dose followed by 4 mg/kg, cohort II) and three-weekly schedule (cohort III). The PK analysis was performed in 18 pts (4 pts receiving the loading dose of cohort III, 8 pts receiving the maintenance dose of cohort III, 3 pts receiving the maintenance dose of cohort II, and 3 pts receiving loading dose of cohort I). Of the 18 pts analyzed, 9 were metastatic. The median age was 54 years (range 39–76), the median weight was 61,5 kg (range 53–80). At diagnoses, 10 pts had stage I disease, 5 and 3 pts had stage II and III respectively, ER was negative in 10 pts and PgR was negative in 12 pts; Ki67 was highly expressed in 14 pts; Her/neu was overexpressed and amplified in 16 and 2 pts respectively. To evaluate preliminary interpatient variability, 3 pts receiving 6mg/kg of trastuzumab repeated the PK analysis after four cycles: the comparison between two groups was not statistically significative. Comparison of Cmax and AUC mean between groups was statistically significative (P<0.05, Bonferroni test) except for 8 mg/kg vs 6 mg/kg AUC.All the doses and schedules analysed are able to reach the minimum serum concentration of trastuzumab that causes the maximal tumor growth inhibition.

[Table: see text]

No significant financial relationships to disclose.
Long-term toxicity of high-dose sequential chemotherapy with autologous hematopoietic stem cells support in very high-risk early breast cancer patients (pts)
Authors: Bernardi A. , Zamagni C. , Quercia S. , Massari F. , Cacciari N. , Martoni A. A.
Published: March 2020

11101

Background: High-dose chemotherapy with autologous haematopoietic stem cells support (HDCT) in the adjuvant treatment of breast cancer has been abandoned by many, but it remains unclear the real role of this treatment and a meta-analysis of high-dose chemotherapy adjuvant trials is ongoing. Methods: Twenty-five consecutive high risk early breast cancer pts with at least 40 months of follow-up treated at our institution with HDCT are included in the present analysis. Median age was 44 (range 24–59 years) and 15 pts were premenopausal. The median number of axillary lymph-nodes metastases was 13 (range 3–49) and the pathological stage was IIB in one pt, IIIA in 3 pts, IIIB in one pt and IIIC in 20 pts. Estrogen and/or progesterone receptors were positive in 15 pts and both negative in 10 pts. The 10- year risk of relapse of pts with disease characteristics similar to those included in our study population is 80–85%. The HDCT regimen used was cyclophosphamide 7g/m2 plus G-CSF (followed by apheresis of peripheral haematopoietic stem cells), methotrexate 8 g/m2 followed by thiotepa 600 mg/m2 and melphalan 160 mg/m2 or by mitozantrone 60 mg/m2 and melphalan 180 mg/m2 and stem cells reinfusion. Results: At a median follow-up of 7 years (range 3,5 - 8 years) 13 pts (52%) relapsed and 10 pts (40%) died. The most common sites of recurrence were lung, liver and bones; 6 pts developed brain metastases and in 2 cases a bone marrow infiltration was documented. No toxic deaths and no long term toxicities, except irreversible amenorrhoea in all the premenopausal pts, were observed. No secondary malignancies occurred.The median relapse-free survival is 65,1 months, while the median overall survival has not been reached yet. Conclusions: In our experience high-dose sequential chemotherapy with autologous stem cells support is a safe treatment with no toxic deaths and no long-term toxicities. This regimen should therefore be further investigated if translational research will be able to identify subgroups of pts with the highest probability to benefit from intensive chemotherapy.

No significant financial relationships to disclose.
Vorinostat (suberoylanilide hydroxamic acid) as salvage therapy in metastatic breast cancer (MBC): A California Cancer Consortium phase II study
Authors: Luu T. H. , Leong L. , Morgan R. , McNamara M. , Lim D. , Portnow J. , Frankel P. , Aparicio A. , Chew H. , Gandara D. R. , Somlo G.
Published: March 2020

11502

Background: MBC patients (pts) have a median survival of 27 mo. Vorinostat is a small molecule inhibitor of histone deacetylase that exerts its targeted action during post-translational acetylation of core nucleosomal histones, affecting chromatin structure, thereby regulating genes implicated in cell survival, proliferation, differentiation, and apoptosis. The primary end point was to evaluate the response rate. Secondary endpoints included: time to progression, overall survival, toxicity, and assessment of biologic correlates. Method: From 6/05 to 3/06, we enrolled 14 pts with measurable MBC. Response and progression were evaluated using RECIST criteria. Two pts had no, 5 pts had one, and 7 pts had two prior regimens. Median age was 60.5 years (37- 89). Six were ER/PR positive, four were Her2neu overexpressers. Sites of metastatic disease included brain (1), liver, lungs, and bone (5), pelvic and chest wall (1), liver and bone (2), distant lymph nodes (3), pleura and bone (1). Pts received Vorinostat 200mg oral twice daily for 14 of 21 days per cycle. Tumor measurements were performed after every 2 cycles. Biopsies (pre and on-treatment) were collected from 6 of 14 pts. Results: The mean cycles delivered was 5 (range: 1–18). Four pts had SD for a median of >8.7 mo (4–13 mo); 1 pt with ER/PR/Her2neu negative tumor who received no prior treatment for MBC to mediastinal nodes and chest wall continues to receive treatment having completed cycle 18 with stable disease for >11.4 mo. The median duration on treatment for all pts is 3.2 mo (1–12 mo). Toxicities included gr 3 fatigue (1), gr 2–3 diarrhea (3), gr 2–3 nausea (2), gr 2 mucositis(1), gr 4 lymphopenia (1), gr 2–3 lymphopenia (6). Correlative studies of pre- and on-treatment tumor samples will be presented describing gene expression profiling using custom Agilent oligonucleotide microarrays optimized for analysis of RNA isolated from formalin fixed paraffin embedded tissues (FFPET). Conclusion: In this trial Vorinostat demonstrated disease stabilization rate in 4/14 (29%) pts by intention to treat analysis. With ease of administration, further investigation in combination with other agents is warranted. (NCI-NO1-CM- 62209)

No significant financial relationships to disclose.