Definitive Breast Cancer Surgery Research Articles

Low RNA disruption during neoadjuvant chemotherapy predicts pathologic complete response absence in patients with breast cancer.

In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in pCR responders than in patients without pCR post-treatment (P = .008). Moreover, maximum tumor RDI values ≤3.7 during treatment predicted for a lack of pCR at surgery (negative predictive value = 93.3%). These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly permitting treatment optimization.

Persistent post-surgical pain following breast cancer surgery: An observational study in a tertiary care hospital.

To determine the frequency of persistent pain in patients after breast cancer surgery, and to assess the distribution and characteristics of pain in such patients. The prospective observational single cohort study was conducted at the Department of Anaesthesiology and in the Breast Clinic of the Department of Surgery, Aga Khan University Hospital, Karachi, from August 2016 to January 2017, and comprised adult female patients with biopsy-proven carcinoma of breast who were scheduled for elective definitive breast cancer surgery. The patients were followed up for up to three months post-surgery and those with persistent pain were followed up for six months post-operation. Data was analysed using SPSS 19. Of the 120 patients, 26(21.7%) developed persistent post-surgical pain for up to three months, while in 17(14.2%) patients, the pain continued for up to six months after the operation. Among those with persistent post-surgical pain, 11(42.3%) had burning pain, 10(38.5%) had throbbing pain, 3(11.5%) had numbness and 2(7.7%)had mixed character of pain. Also, 11(42.3%)patients developed pain at more than one site including axilla, chest wall, upper arm and surgical scar area, and the site of pain in majority patients 15(57.7%) was axilla. The incidence of persistent pain following breast cancer surgery was found to be 21.7%.

Abstract GS6-05: The impact of breast cancer surgery on quality of life: Long term results from E5103

Abstract Background: Breast cancer (BC) treatment, including surgery, can impact not only short-term health outcomes but may also affect longer term health-related and psychosocial quality of life (QOL). We sought to describe the impact of BC surgery on QOL among breast cancer survivors followed in a large randomized trial. Methods: The ECOG-ACRIN protocol E5103 was a phase III trial that randomized BC patients (pts) who had undergone definitive BC surgery to receive adjuvant doxorubicin, cyclophosphamide, and paclitaxel with either bevacizumab (bev) or placebo. Telephone based surveys were administered to all pts enrolled between 01/Jan/10 and 08/Jun/10 as part of a Decision-Making/QOL component until 18 mos post enrollment. Functional/psychosocial QOL domains were assessed by the EQ-5D-3L and the FACT B+G. Fisher's exact test compared categorical and Wilcoxon rank sum test compared continuous variables between subgroups. Multivariable regression was used to evaluate factors in addition to primary surgery at enrollment (age, race, ER/PgR status, tumor size, nodal status) associated with overall FACT score at 18 mos. Results: Patient reported outcomes at 18 mos were available from 89.6% (465/519) pts. At enrollment, 57% (266/465) had a mastectomy; 43% (199/465) breast conserving surgery (BCS). Median age at enrollment was 52 (range: 25-76) years. There were no differences in QOL between bev vs placebo treatment arms (EQ-5D-3L Index Score p=0.65; FACT B+G Score p=0.23) at 18 mos so groups were combined. Using EQ-5D-3L, over half of the pts (58%) reported at least some pain/discomfort; 38% symptoms of anxiety/depression. A higher proportion of mastectomy pts reported problems with usual activities compared to BCS pts (Table). Compared to BCS pts, mastectomy pts had lower average EQ5D-3L scores 0.80 vs. 0.84, p=0.04 and FACT B+G scores 109 vs. 114, p=0.01, indicating worse QOL. In univariate analyses, non-white race (p=0.03), ER/PgR+ status (p=0.04) and mastectomy as primary surgery (p=0.01) were significantly associated with worse QOL (lower FACT B+G scores). In multivariable analyses, non-white race (p=0.02) and ER/PgR+ status (p=0.05) remained associated with worse QOL; mastectomy was borderline significant (p=0.06). Conclusions: Among women participating in a contemporary adjuvant BC chemotherapy trial, a substantial proportion of survivors experience symptoms that may be amenable to intervention, including referral to physical rehabilitation, especially among pts undergoing more extensive surgery. Attention to psychosocial health is also essential both during and after completion of active treatment to optimize QOL outcomes. N(%) reporting problems* 5 DimensionsBCSMastectomyOverallp**Mobility44(23)59(23)103(23)1.00Self-care11(6)23(9)34(7)0.21Usual activities49(25)90(34)139(30)0.04Pain/discomfort104(53)161(61)265(58)0.08Anxiety/depression70(36)105(40)175(38)0.44*3L: 3 possible answers: 1) no problems 2) some/moderate problems 3) problems; responses then collapsed into no problems vs. any problems' (=some/moderate problems and problems). ** Fisher's exact test p-value. Citation Format: Rosenberg SM, O'Neill A, Sepucha K, Miller KD, Dang CT, Northfelt DW, Sledge GW, Schneider BP, Partridge AH. The impact of breast cancer surgery on quality of life: Long term results from E5103 [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS6-05.

Impact of Genomic Assay Testing and Clinical Factors on Chemotherapy Use After Implementation of Standardized Testing Criteria.

For clinically appropriate early-stage breast cancer patients, reflex criteria for Oncotype DX ordering ("the intervention") were implemented at our comprehensive cancer center, which reduced time-to-adjuvant chemotherapy initiation. Our objective was to evaluate Oncotype DX ordering practices and chemotherapy use before and after implementation of the intervention. We examined medical records for 498 patients who had definitive breast cancer surgery at our center. The post-intervention cohort consisted of 232 consecutive patients who had Oncotype DX testing after reflex criteria implementation. This group was compared to a retrospective cohort of 266 patients who were diagnosed and treated prior to reflex criteria implementation, including patients who did and did not have Oncotype DX ordered. Factors associated with Oncotype DX ordering pre- and post-intervention were examined. We used multivariate logistic regression to evaluate factors associated with chemotherapy receipt among patients with Oncotype DX testing. The distribution of Oncotype DX scores, the proportion of those having Oncotype DX testing (28.9% vs. 34.1%) and those receiving chemotherapy (14.3% vs. 19.4%), did not significantly change between pre- and post-intervention groups. Age ≤65 years, stage II, grade 2, 1-3+ nodes, and tumor size >2 cm were associated with higher odds of Oncotype DX testing. Among patients having Oncotype DX testing, node status and Oncotype DX scores were significantly associated with chemotherapy receipt. Our criteria for reflex Oncotype DX ordering appropriately targeted patients for whom Oncotype DX would typically be ordered by providers. No significant change in the rate of Oncotype DX ordering or chemotherapy use was observed after reflex testing implementation. This study demonstrates that implementing multidisciplinary consensus reflex criteria for Oncotype DX ordering maintains a stable Oncotype DX ordering rate and chemotherapy rate, mirroring what was observed in a specific clinical practice, while decreasing treatment delays due to additional testing. These reflex criteria appropriately capture patients who would likely have had Oncotype DX ordered by their providers and for whom the test results are predicted to influence management. This intervention serves as a potential model for other large integrated, multidisciplinary oncology centers to institute processes targeting patient populations most likely to benefit from genomic assay testing, while mitigating treatment delays.

Adherence to Guidelines for Breast Surveillance in Breast Cancer Survivors.

Background: Guidelines recommend annual mammography after curative-intent treatment for breast cancer. The goal of this study was to assess contemporary patterns of breast imaging after breast cancer treatment. Methods: Administrative claims data were used to identify privately insured and Medicare Advantage beneficiaries with nonmetastatic breast cancer who had residual breast tissue (not bilateral mastectomy) after breast surgery between January 2005 and May 2015. We calculated the proportion of patients who had a mammogram, MRI, both, or neither during each of 5 subsequent 13-month periods. Multinomial logistic regression was used to assess associations between patient characteristics, healthcare use, and breast imaging in the first and fifth years after surgery. Results: A total of 27,212 patients were followed for a median of 2.9 years (interquartile range, 1.8-4.6) after definitive breast cancer surgery. In year 1, 78% were screened using mammography alone, 1% using MRI alone, and 8% using both tests; 13% did not undergo either. By year 5, the proportion of the remaining cohort (n=4,790) who had no breast imaging was 19%. Older age was associated with an increased likelihood of mammography and a decreased likelihood of MRI during the first and fifth years. Black race, mastectomy, chemotherapy, and no MRI at baseline were all associated with a decreased likelihood of both types of imaging. Conclusions: Even in an insured cohort, a substantial proportion of breast cancer survivors do not undergo annual surveillance breast imaging, particularly as time passes. Understanding factors associated with imaging in cancer survivors may help improve adherence to survivorship care guidelines.

Psychological outcomes and surgical decisions after genetic testing in women newly diagnosed with breast cancer with and without a family history.

In patients with early breast cancer, personal and tumour characteristics other than family history are increasingly used to prompt genetic testing to guide women's cancer management (treatment-focused genetic testing, 'TFGT'). Women without a known strong family history of breast and/or ovarian may be more vulnerable to psychological sequelae arising from TFGT. We compared the impact of TFGT in women with (FH+) and without (FH-) a strong family history on psychological adjustment and surgical decisions. Women aged <50 years with high-risk features were offered TFGT before definitive breast cancer surgery and completed self-report questionnaires at four time points over 12 months. All 128 women opted for TFGT. TFGT identified 18 carriers of a disease-causing variant (50.0% FH+) and 110 non-carriers (59.1% FH+). There were no differences based on family history in bilateral mastectomy (BM) uptake, p = .190, or uptake of risk-reducing bilateral salpingo-oophorectomy (RRBSO), p = .093. FH- women had lower decreases in anxiety a year after diagnosis, p = .011, and regret regarding their decision whether to undergo BM, p = .022, or RRBSO, p = .016 than FH + women. FH- carriers reported significantly higher regret regarding their TFGT choice (p = .024) and test-related distress (p = .012) than FH + carriers, but this regret/distress could not be attributed to a concern regarding a possible worse prognosis. These findings indicate that FH- women may require additional counselling to facilitate informed decisions. Carriers without a family history may require additional follow-up counselling to facilitate psychological adjustment to their positive variant results, extra support in making surgical decisions, and counselling about how best to communicate results to family members.

Abstract OT2-01-02: A pilot study to evaluate preoperative localization of breast and axillary lesions in neoadjuvant patients 31-365 days prior to surgery

Abstract SCOUT standard of care preoperative localization has been used in over 300 breast cancer patients at our hospital and over 12,000 breast cancer patients in 100 US sites between June 2015-May 2017. The radiologist performs SCOUT localization with Mammography, Ultrasound or CT guidance 0- 30 days prior to surgery. In this study, we will evaluate the performance of SCOUT over longer duration (31 - 365 days) to address the needs of patients who require neoadjuvant treatment prior to definitive surgery. Placement of SCOUT localization prior to treatment response, when the lesion is clearly visualized on imaging, should be more accurate. Successful neoadjuvant treatment, which results in a complete or partial response often renders preoperative image-guided localization by the radiologist a more difficult and less reliable procedure and can result in unintended larger, more disfiguring breast cancer surgery. This pilot study will assess whether placement of the SCOUT prior to neoadjuvant treatment allows for longer-term preoperative localization of breast/axillary lesions. Successful performance with no significant adverse events may prove valuable to future patients who will require fewer and/or less extensive preoperative and surgical procedures. Some value may also be provided to subjects as the targeting before tumor shrinkage is expected to be more accurate. Trial design Radiologists perform SCOUT localization using Mammography, Ultrasound or CT guidance 31 - 365 days preoperatively. Surgeons use the SCOUT system to locate and excise the SCOUT and target tissue. Eligibility criteria The study population consists of 25 - 35 adult surgical patient volunteers who plan to have definitive breast cancer surgery at our hospital after neoadjuvant treatment. Subject Inclusion Criteria · Female patient 18 - 90 years old · Patient is willing and able to comply with all study procedures and follow-up (1 - 13 months) · SCOUT localization is performed before neoadjuvant treatment begins. Subject Exclusion Criteria · Patient is pregnant, has a pacemaker or implantable defibrillators · Patient has known or suspected nickel allergy · Patient is receiving an investigational drug that could potentially confound assessment of adverse device events Statistical methods This pilot study will provide an estimate for the efficacy of the method. Simple statistics will be used to evaluate primary and secondary endpoint data. Primary Endpoint The primary endpoint of this study is successful surgery, defined as a SCOUT localization at the target lesion, which remains in place 31 - 365 days preoperatively, and can successfully be removed with target tissue during surgery. Secondary Endpoints · Number of days prior to surgery (31 - 365) that the SCOUT is placed by the radiologist to localize the target breast / axillary tissue. · Success rate of preoperative SCOUT placement by radiologist and SCOUT stability (within 1 cm of the center of the target tissue) for 31- 365 days. ClinicalTrials.gov identifier: NCT03015649 Contact information Mary Hayes, MD Present accrual/target accrual: 4/30. Citation Format: Hayes MK, Bloomquist EV, Wright HR. A pilot study to evaluate preoperative localization of breast and axillary lesions in neoadjuvant patients 31-365 days prior to surgery [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr OT2-01-02.

Streamlined genetic education is effective in preparing women newly diagnosed with breast cancer for decision making about treatment-focused genetic testing: a randomized controlled noninferiority trial.

Increasingly, women newly diagnosed with breast cancer are being offered treatment-focused genetic testing (TFGT). As the demand for TFGT increases, streamlined methods of genetic education are needed. In this noninferiority trial, women aged <50 years with either a strong family history (FH+) or other features suggestive of a germ-line mutation (FH-) were randomized before definitive breast cancer surgery to receive TFGT education either as brief written materials (intervention group (IG)) or during a genetic counseling session at a familial cancer clinic (usual-care group (UCG)). Women completed self-report questionnaires at four time points over 12 months. A total of 135 women were included in the analysis, all of whom opted for TFGT. Decisional conflict about TFGT choice (primary outcome) was not inferior in the IG compared with the UCG (noninferiority margin of -10; mean difference = 2.45; 95% confidence interval -2.87-7.76; P = 0.36). Costs per woman counseled in the IG were significantly lower (AUD$89) compared with the UCG (AUD$173; t(115) = 6.02; P < 0.001). A streamlined model of educating women newly diagnosed with breast cancer about TFGT seems to be a cost-effective way of delivering education while ensuring that women feel informed and supported in their decision making, thus freeing resources for other women to access TFGT.Genet Med 19 4, 448-456.

Abstract P1-10-01: Are physicians "choosing wisely" when imaging for distant metastases in women with early stage (1 or 2) breast cancer? A population study

Abstract Background: The probability of detecting radiologically evident distant metastases in asymptomatic patients with early stage (stage 1 and 2) breast cancer (BC) is low. Published guidelines, including the 2012 American Society of Clinical Oncology (ASCO) "Top-5" recommendation for "choosing wisely" in oncology, recommend against imaging in these patients. Imaging is also associated with significant false positive results and the need for additional confirmatory imaging and/or invasive procedures. Despite this evidence-base, imaging continues to be over-utilized. We decided to quantify the rates of staging imaging in women with early breast cancer in Canada’s largest province to determine whether provincial practice patterns are in keeping with the spirit of the guidelines and the 2012 ASCO "Top-5" recommendation. Methods: Provincial registry data available through the Institute for Clinical Evaluative Sciences were used to identify all patients with a first diagnosis of stage 1 and 2 breast cancer who underwent breast cancer surgery. For each patient, all imaging of the most common metastatic sites (i.e. skeleton, thorax and abdomen) was captured from the date of diagnosis up until 3 months after definitive breast cancer surgery. Patients who received neoadjuvant therapy or with a prior history of any invasive malignancy were excluded. Results: Between 2007 and 2012, 27,236 patients with stage 1 and 2 BC were identified. Overall data are shown in the table: StageNo. of patients% having at least one imaging test (total)Total no. of imaging tests (mean per patient imaged)% of patients imaged who required confirmatory imaging (total)No. of confirmatory imaging tests performed (% of total imaging)114,11383% (11,713)40,464 (3.5)55% (6,420)11,202 (28%)213,12394% (12,330)53,729 (4.4)65% (7,983)16,292 (30%) The most common initial (i.e. not confirmatory) imaging modalities of the skeleton, thorax and abdomen, for both groups were, bone scan (19%; 12,799/66,699), chest x-ray (28%; 18,789/66,699) and abdominal ultrasound (20%; 13,387/66,699) respectively. Use of advanced imaging (isotope bone scans, CT, MRI, PET) to look at potential sites of metastasis represented 38% (11,063/29,262) and 46% (17,180/37,437) of initial imaging tests in stage 1 and 2 BC patients respectively. Conclusion: Imaging for distant metastatic disease in patients with stage 1 and 2 BC is commonly performed in Ontario despite multiple guidelines recommending against this. Advanced imaging (isotope bone scans, CT, MRI, PET) is commonly used as the initial imaging modality of choice. Of particular concern is the fact that 60% (14,403/24,043) of BC patients with early stage disease who were imaged required some form of confirmatory imaging. These results show the importance of the recent ASCO "Top-5" recommendation against staging imaging in such patients. The reasons for this disconnect between evidence and practice are not fully understood, but knowledge translation strategies beyond publishing guidelines or recommendations are required if we are to elicit a meaningful and sustained change in physician practice. Citation Format: Demetrios Simos, Christina Catley, Carl vanWalraven, Ian D Graham, Dean Fergusson, Angel Arnaout, Susan Dent, Mark Clemons. Are physicians "choosing wisely" when imaging for distant metastases in women with early stage (1 or 2) breast cancer? A population study [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P1-10-01.

Disparities in breast cancer surgery delay: the lingering effect of race.

Delays to surgical breast cancer treatment of 90 days or more may be associated with greater stage migration. We investigated racial disparities in time to receiving first surgical treatment in breast cancer patients. Insured black (56 %) and white (44 %) women with primary breast cancer completed telephone interviews regarding psychosocial (e.g., self-efficacy) and health care factors (e.g., communication). Clinical data were extracted from medical charts. Time to surgery was measured as the days between diagnosis and definitive surgical treatment. We also examined delays of more than 90 days. Unadjusted hazard ratios (HRs) examined univariate relationships between delay outcomes and covariates. Cox proportional hazard models were used for multivariate analyses. Mean time to surgery was higher in blacks (mean 47 days) than whites (mean 33 days; p = .001). Black women were less likely to receive therapy before 90 days compared to white women after adjustment for covariates (HR .58; 95 % confidence interval .44, .78). Health care process factors were nonsignificant in multivariate models. Women with shorter delay reported Internet use (vs. not) and underwent breast-conserving surgery (vs. mastectomy) (p < .01). Prolonged delays to definitive breast cancer surgery persist among black women. Because the 90-day interval has been associated with poorer outcomes, interventions to address delay are needed.

Feasibility of fast track discharge in breast cancer patients undergoing definitive surgery and impact on quality of life: a prospective study from tertiary care center in India.

To evaluate the feasibility and impact of fast track discharge in patients undergoing definitive breast cancer surgery. One hundred six breast cancer patients older than 20 years of age were assigned to undergo definitive breast cancer surgery. It was ensured that enrolled patients had a ready access to hospital, reasonable home circumstances. They were assessed by using post-anesthesia discharge scoring system (PADSS) for fast track discharge. Quality of life both in preoperative and postoperative period was assessed by Functional Assessment of Cancer Therapy-Breast cancer version 4 (FACT-B4) questionnaires. Overall 90 patients (84.9%) were fit for fast track discharge. Eighty-nine patients (83.96%) were successfully discharged within 48 hr. One patient (0.94%) could not be discharged despite being fit as she was of concern that it would put too much responsibility on the family. Mean duration of postoperative hospital stay in patients fit for fast track surgery was 42.27 ± 5.73 hr with a median of 44 hr. All patients undergoing breast conservation could be discharged on fast track basis with a mean postoperative hospital stay of 32.12 hr. Fast track discharges in breast cancer patients after definitive surgery are feasible in Indian setting.

Abstract 2630: Simvastatin induced apoptosis and suppressed proliferation of breast cancer through deactivating PI3K/Akt/mTOR pathway

Abstract PURPOSE: Statins, inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, purportedly exert anti-tumoral effects on breast cancer by increasing apoptosis and decreasing proliferation. However, the biologic mechanisms for these actions are not fully elucidated. The aim of this study was to explore the effects of simvastatin on apoptosis, proliferation and commonly abrogated PI3K/Akt/mTOR pathway in a window-of-opportunity breast cancer trial and breast cancer cell lines. EXPERIMENTAL DESIGN: A total of 16 female patients with newly diagnosed primary breast cancer were recruited into a preoperative window-of-opportunity trial. Patients received simvastatin for 10-28 days at a dose of 20mg daily before definitive breast cancer surgery. Pre- and post-treatment tumor biopsies were obtained for immunohistochemistry staining for cleaved caspase 3, Ki67, Pten, phospho-Akt and phospho-S6 ribosomal protein, and the changes between paired pre- and post-treatment tumors compared. For in vitro functional studies, apoptosis and proliferation assays were performed on breast cancer cell lines MCF7 and MDA-MB-231 48 hours after treatment with simvastatin. Using Western blots, the effects of simvastatin on apoptosis protein caspase 3, cell cycle proteins of c-myc, cyclin D1, p21 and p27, and of PI3K/Akt/mTOR pathway through phosphorylation of Akt, mTOR, p70S6K, S6 ribosomal protein and 4EBP1, were assessed. RESULTS: In the prospective clinical trial, simvastatin treatment led to significant increase in apoptosis in post-treatment tumors, as determined by positive cleaved caspase 3 (23.4±24.3 vs 8.9±7.4, p=0.002). Decreased trend for proliferation was also observed in post-treatment tumors (57.7±35.2 vs 74.6±59.9 for Ki67, p=0.245). Moreover, simvastatin treatment markedly suppressed PI3K/Akt/mTOR signalling pathway by activating Pten (66.1±65.2 vs 30.0±46.6, p=0.005) and by dephosphorylating Pten downstream effectors, Akt and S6 ribosomal protein (9.0±19.5 vs 93.0±87.4, p=0.002 for phospho-Akt; 63.7±51.6 vs 108.6±67.7, p=0.033 for phospho-S6 ribosomal protein). In MCF7 and MDA-MB-231 cells, simvastatin treatment similarly induced apoptosis and inhibited cell proliferation, with decrease in expression of c-myc and cyclin D1 and increase in cell cycle suppressor p21 and p27 at a dose dependent manner. Moreover, simvastatin treatment, at 20uM for MCF7 and 400nM for MDA-MB-231 cells, strongly suppressed sequential phosphorylation of PI3K/Akt/mTOR pathway cascades including Akt, mTOR, p70S6K, S6 ribosomal protein and 4EBP1. CONCLUSION: The clinical trial and in vitro functional studies concordantly showed simvastatin to promote apoptosis, suppress proliferation and dephosphorylate sequential signalling cascades of PI3K/Akt/mTOR pathway of breast cancer. These findings shed light on the biological and potential anti-tumor effects of simvastatin in breast cancer. Citation Format: Tingting Wang, Serena Seah, Ching-Wan Chan, Mikael Hartman, Nyein Nyein Thaw Dar, Philip Iau, Boon-Cher Goh, Soo-Chin Lee. Simvastatin induced apoptosis and suppressed proliferation of breast cancer through deactivating PI3K/Akt/mTOR pathway. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2630. doi:10.1158/1538-7445.AM2014-2630

Sentinel lymph node biopsy before mastectomy and immediate breast reconstruction does not significantly delay surgery in early breast cancer.

Sentinel lymph node biopsy (SLNB) before mastectomy and immediate breast reconstruction (IBR) may help to avoid the negative cosmetic effects of radiotherapy on reconstructed breasts in lymph node-positive patients. Concerns have been raised regarding possible delays whilst awaiting the SLNB result prior to definitive surgery, which needs to be performed within 31 days of cancer diagnosis. The aim was to investigate whether initial SLNB delays mastectomy and IBR. All patients who had IBR between January 2005 and 2007 were reviewed retrospectively. Before October 2005 axillary staging was performed simultaneously with mastectomy and IBR (Group I). After October 2005, SLNB was performed as an initial procedure and patients with positive SLNB were only offered a temporary tissue expander to be replaced by autogenous reconstruction after completing the cancer treatment (Group II). Date of diagnosis and waiting times were recorded and the two groups were compared. Different reasons for delays in treatment were studied. One hundred and thirty-nine IBR (123 patients) were included in the statistical analysis (67 IBR in Group I and 72 IBR in Group II). Seventy-one patients (57.7%) had no delay (mean waiting time of 23 days). Fifty-two patients (42.3%) had delay longer than 31 days (mean waiting time of 66 days). Group I patients had a mean waiting time (standard deviation) of 38.8 (38) days and Group II patients 42.7 (24) days (p = 0.51). In this group of patients, SLNB before mastectomy and IBR does not significantly delay definitive breast cancer surgery.

Clinicopathologic characteristics of breast cancer in Jamaica.

Breast cancer is the most common cancer in Jamaican women. This study assessed the clinicopathologic features of cases in a hospital-based specialist clinic in Kingston, Jamaica. A retrospective chart review was performed for the 2-year study period and relevant clinical and surgico-pathologic data were recorded and analyzed. Median age of the 121 breast cancer patients was 52 years (range 22-84, IQR 20) and there was 1 case of male breast cancer. Most patients (65%) were referred from the surgical service after definitive breast cancer surgery, 20% were referred for pre-operative systemic therapy, and 15% had a diagnosis of metastatic disease. The surgico-pathologic group comprised 78 women who were referred for adjuvant therapy. The majority had presented with a palpable breast lump (91%), with median tumour size 3.5cm (range 0.4-13, IQR 4). Most tumours were node positive (56%). Approximately one-third of patients had stage III disease (33%). Most women presented with large palpable tumours and had lymph node involvement confirmed on surgicopathological evaluation, indicative of limited early breast cancer detection. A national screening mammography programme is recommended for detection of earlier lesions. Pre-operative systemic therapy should be considered as an option for eligible patients.

Race of the Clock: Reducing Delay to Curative Breast Cancer Surgery

Analysis of Moffitt Cancer Center data on time from breast biopsy to first definitive surgery showed an average of 6.9 weeks, which concerned the breast program faculty members. Delays in curative surgery may impact mortality, quality of life, and time to adjuvant therapy. The purpose of this study was to analyze steps from breast biopsy to definitive breast cancer surgery and to develop proposals and strategies for improvement. Data were collected from various sources, including the tumor registry, patient appointment system, tumor board lists, and the NCCN Oncology Outcomes Database for Breast Cancer. Three phases of the surgical process were identified with regard to lead time: biopsy to first consult (BX-FC); first consult to tumor board (FC-TB); and tumor board to surgery (TB-SU). Other factors, including operating room capacity and schedules, were also evaluated. The greatest percentage of total lead time occurred in the TB-SU phase (52% vs 35% in BX-FC, and 13% in FC-TB phases). The longest average lead time, 3.6 weeks, was also in the TB-SU phase. The TB-SU time was greatest when surgery was scheduled after tumor board and if surgery required breast reconstruction. Limitation of physician capacity was a major factor in treatment delay. The Opportunity for Improvement project enabled institutional analysis of the need for quality improvement in time for curative surgery for breast cancer. A significant factor that created time delay was physician capacity. As a result, additional faculty and staff have been recruited. A new expanded facility is currently in progress that will provide more physical space and services.

Adopting ambulatory breast cancer surgery as the standard of care in an asian population.

Introduction. Ambulatory surgery is not commonly practiced in Asia. A 23-hour ambulatory (AS23) service was implemented at our institute in March 2004 to allow more surgeries to be performed as ambulatory procedures. In this study, we reviewed the impact of the AS23 service on breast cancer surgeries and reviewed surgical outcomes, including postoperative complications, length of stay, and 30-day readmission. Methods. Retrospective review was performed of 1742 patients who underwent definitive breast cancer surgery from 1 March 2004 to 31 December 2010. Results. By 2010, more than 70% of surgeries were being performed as ambulatory procedures. Younger women (P < 0.01), those undergoing wide local excision (P < 0.01) and those with ductal carcinoma-in situ or early stage breast cancer (P < 0.01), were more likely to undergo ambulatory surgery. Six percent of patients initially scheduled for ambulatory surgery were eventually managed as inpatients; a third of these were because of perioperative complications. Wound complications, 30-day readmission and reoperation rates were not more frequent with ambulatory surgery. Conclusion. Ambulatory breast cancer surgery is now the standard of care at our institute. An integrated workflow facilitating proper patient selection and structured postoperativee outpatient care have ensured minimal complications and high patient acceptance.

Pretest genetic counseling informs patients withBRCAmutation

When patients with breast cancer received pretest genetic counseling before undergoing definitive surgery for breast cancer, they showed fewer signs of distress. At the same time, patients who were offered counseling after surgery improved their informed decision-making, while both groups were better informed, according to a study by researchers at the H. Lee Moffitt Cancer Center and Research Institute in Tampa, Florida. The study, funded by the American Cancer Society, was published in the Annals of Surgical Oncology.1 The researchers note that patients with breast cancer with certain risk factors likely would benefit from pretest genetic counseling and genetic testing at or near the time of their initial diagnosis. Although some health care providers may fear that these efforts could increase distress for patients at this time, few studies to date have actually examined the impact of such pretest genetic counseling, according to lead coauthor Susan Vadaparampil, PhD, MPH, an associate member of the Health Outcomes and Behavior Program at H. Lee Moffitt. She and her colleagues developed a study to determine how pretest counseling impacts cancer knowledge, psychosocial development, and decision-making about genetic testing for patients with breast cancer. They analyzed 103 patients, 87 of whom had undergone surgery and 16 of whom had not. The patients ranged in age from 24 years to 69 years. They met with master's degree-level, trained genetic health professionals to obtain a risk assessment based on their personal and family genetic history. At the same time, they received information about hereditary breast and ovarian cancer as well as the limitations of genetic testing. The study found that both the before-surgery and aftersurgery groups experienced increases in cancer knowledge after pretest genetic counseling. At the same time, the before-surgery group reported decreases in cancer-related distress and intrusive thoughts. Furthermore, informed decision-making in the after-surgery group improved. Dr. Vadaparampil stresses that before-surgery genetic counselors may need to focus on perceived risks of genetic testing and how they might align with patients' values. Reference

Clinical outcome of preoperative breast MRI for early-stage breast cancer.

42 Background: Preoperative breast magnetic resonance imaging MRI is used in clinical practice to improve oncologic outcome of breast cancer. Concerns over increased rate of unnecessary mastectomies and additional biopsies have been raised. The purpose of our study is to review the outcome of preoperative breast MRI at our institution. Methods: The current study is a retrospective review of 215 patients with early stage breast cancer who underwent definitive surgery. Breast MRI is being used at our institution within the context of multidisciplinary approach. Patients who had complete clinical, radiologic, and pathological data available were identified and formed the basis of this analysis. Results: 215 patients were diagnosed with breast cancer stage I-II in the period of 2006-2012 and had complete data for review. 92 patients out of 215 (43%) had breast MRI prior to definitive surgery. both groups were different in regard of age. Rate of breast conservative surgery, mastectomies, and re-excision for positive margins was similar in both groups. 6 patients out of 12 patients who had breast MRI and underwent bilateral mastectomies were found to have abnormal pathological findings (DCIS 3, LCIS 1, invasive ductal carcinoma 1, and focal epithelial atypia 1). Time from first diagnostic procedure to definitive surgery was similar in both groups (29 days vs. 27.5 days). 38 (41%) patients out of 92 who had breast MRI underwent additional breast biopsies for suspicious lesions with only 8 (21%) patients found to have abnormal pathological findings. Conclusions: Use of breast MRI prior to definitive surgery for early stage breast cancer was associated with increased rate of additional biopsies for suspicious lesions with no favorable effect on re-excision rate. [Table: see text]

The Effects of P6 Acupressure and Nurse-Provided Counseling on Chemotherapy-Induced Nausea and Vomiting in Patients With Breast Cancer

To evaluate the effects of pericardium 6 (P6) acupressure and nurse-provided counseling on chemotherapy-induced nausea and vomiting (CINV) in patients with breast cancer. Randomized, controlled trial. A university cancer center in Seoul, South Korea. 120 women who were beginning their second cycle of adjuvant chemotherapy after definitive surgery for breast cancer and who had more than mild levels of nausea and vomiting with the first cycle of chemotherapy. Participants were assigned randomly into four groups: control (placebo on SI3), counseling only, P6 acupressure only, and P6 acupressure plus nurse-provided counseling. The experiences of upper-gastrointestinal distress were measured by the Rhodes Index of Nausea, Vomiting, and Retching for acute (day 1) and delayed (day 2 to day 5) CINV. Nausea, retching, vomiting, P6 acupressure, and counseling. No significant differences were found in the demographic and disease-related variables among the four groups. The levels of CINV were significantly different among the groups from day 2 to day 5. The CINV differences were attributed mainly to the difference between the control group and the group with P6 acupressure plus nurse-provided counseling. The effects of acupressure were proven from day 2 to day 5, and the effects of nurse-provided counseling were proven on day 4 and were close to significance level on day 5. Synergic effects of P6 acupressure with nurse-provided counseling appeared to be effective in reducing CINV in patients with breast cancer. P6 acupressure combined with counseling by nurses is a safe and easy-to-apply tool in CINV management in practice.

OT1-02-04: Adjuvant Pertuzumab and Herceptin IN IniTial TherapY of Breast Cancer: APHINITY (BIG 4–11/BO25126/TOC4939g).

Abstract Background Approximately 20% of breast cancer (BC) patients (pts) have HER2−positive tumors. While the adjuvant use of the anti-HER2 humanized monoclonal antibody trastuzumab (T) has been shown to improve disease-free (DFS) and overall survival (OS), not all pts treated with this agent benefit from this therapy. Pertuzumab (P) is a humanized monoclonal antibody that inhibits HER2 dimerization and induces ADCC with a complementary mechanism of action to T. In HER2−positiveadvanced BC, T and P is active in pts who have progressed to T. In the neoadjuvant setting, T and P in combination with chemotherapy (CT) nearly doubled the pathological complete response rate compared to either T or P administered in combination with CT (45.8% vs 29% vs 24%, respectively). Therefore, comprehensive HER2 blockade with two anti-HER2 monoclonal antibodies warrants further investigation in the adjuvant setting. Trial Design: APHINITY is a prospective, randomized, multicenter, double-blind, placebo-controlled study in pts with HER2−positive primary BC who have had an excision of their tumor. Pts will be randomized to one of 2 arms (1:1 ratio). The investigational arm will comprise of a course of adjuvant CT (investigators choice) consisting of either an anthracycline-taxane or taxane-platin containing regimens and T and P for 1 year. The comparator arm will consist of the same adjuvant CT backbone with T and placebo for 1 year. Major Eligibility Criteria: 1. Non-metastatic primary BC histologically confirmed and adequately excised 2. Node-positive or node-negative: for patients with node-positive disease (pN ≥1), any pT except T0; for patients with node-negative disease (pN0), tumor size must be &amp;gt;1.0 cm OR for tumor size between &amp;gt;0.5 cm and ≤1.0 cm, at least one of the following features will be required: histologic grade 3 OR negative for ER and PgR OR age &amp;lt;35 years 3. The interval between definitive surgery for BC and randomization must be at least 3 weeks but no more than 7 weeks 4. Baseline LVEF ≥55% 5. HER2−positive BC confirmed by a central laboratory and defined as: IHC 3+ in &amp;gt;10% immunoreactive cells OR HER2 gene amplification by in situ hybridization [ISH] (ratio of HER2 gene signals to centromere 17 signals ≥2) Aims: The primary objective is to compare invasive disease-free survival (IDFS) between both treatment arms. Secondary objectives include comparing IDFS including second non-BC, DFS, OS, recurrence-free interval (RFI), distant RFI, cardiac safety, overall safety and health-related quality of life in the two treatment arms. Statistical Methods: Pts will be stratified based on nodal status, type of adjuvant CT regimen, hormone receptor status and geographical region. The study is designed to have an 80% power to test the null hypothesis of no true difference in risk of an IDFS event (HR = 1) versus the alternative hypothesis of a difference (HR = 0.75) in hazard rates with a 5%, 2-sided significance level. Target accrual: 3806; Present accrual: Start Q4 2011 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr OT1-02-04.