Chemotherapy For Early Breast Cancer Research Articles

Where Is the Genesis of Pancreatic Cancer? What is the Cause & Is There a Cure?

We present a case of hepatitis B reactivation in a patient receiving adjuvant chemotherapy for early breast cancer. This is a 49-year-old post-menopausal, Chinese female with history of chronic hepatitis B with inactive carrier state, and right invasive ductal carcinoma staged as cT2N1M0, pT2N1aM0, anatomic stage IIB, prognostic stage IIA, estrogen and progesterone receptor positive, and human epidermal growth factor 2 negative. The patient underwent bilateral mastectomy with implant reconstruction and right axillary lymph node dissection followed by adjuvant chemotherapy planned as dose dense doxorubicin and cyclophosphamide (ddAC), followed by dose dense paclitaxel (ddT). Two weeks after her first cycle of dose dense paclitaxel, she developed grade III HBV reactivation with hepatitis. This report highlights HBV reactivation as a potential complication of chemotherapy for solid tumors, and reviews recommended HBV screening, prevention and management of HBV reactivation in this patient population.

Abstract P2-12-11: Does goserelin have an effect on quality of life in women who have chemotherapy for early breast cancer? Results from the OPTION randomised trial

Abstract The OPTION trial examined whether or not premenopausal women with early breast cancer receiving chemotherapy benefited from ovarian function protection with goserelin. This trial showed some preservation of ovarian function and fertility in women aged 40 years or less*. Additionally the OPTION trial examined the immediate and late impact of treatments on patients’ Quality of Life (QoL) over a 5 year period. Patients and Methods: In the OPTION trial 227 pre-menopausal patients with early stage breast cancer were randomly assigned to chemotherapy with or without goserelin. Patients were stratified by age into ≤40 years and > 40 years of age. QoL was assessed with the Functional Assessment of Cancer Therapy - Breast (FACT-B) and Endocrine Symptom checklist(ES) at baseline (pre- treatment), 3, 6, 12, 18 and 24 months, then annually to 5 years. Results:-Two hundred and thirteen patients were available for analysis of QoL results. There was a temporary increase in endocrine symptoms of menopause in the goserelin group that was statistically higher than in the controls (P = 0.02) and was associated with a decrease in the main outcome measure of global QoL, TOI. This contrasted with a longer term outcome favouring the intervention in terms of QoL and fewer adverse endocrine symptoms, though these later findings were not statistically significant. Conclusions: Cytotoxic chemotherapy with or without goserelin causes a short term decrement in QoL for up to 6 months in otherwise well women.* Ann Onc 2017 28 1811-1816. Citation Format: Robert CF Leonard, Janine Mansi, Ann Yellowlees, Lesley Fallowfield, Valerie Jenkins. Does goserelin have an effect on quality of life in women who have chemotherapy for early breast cancer? Results from the OPTION randomised trial [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-12-11.

Abstract P3-08-48: Adiposity, comorbidities, and function in patients with early breast cancer

Abstract Introduction: Visceral adipose tissue (VAT) is correlated with lower overall survival and higher chemotherapy toxicity in women with breast cancer (Del Fabbro 2012, Feliciano 2019). In a sample of women scheduled for chemotherapy for early breast cancer (EBC) (stage I-III), we evaluate whether VAT or superficial adipose tissue (SAT) are associated with comorbidities, function, and clinically-used body metrics, Body Mass Index (BMI) and Body Surface Area (BSA).Methods: Women age 21 or older were enrolled in intervention studies (NCT02167932, NCT02328313) to encourage home-based walking during chemotherapy for EBC. Prior to chemotherapy initiation, patients had abdominal computerized tomography (CT) scans and completed Timed Up and Go (TUG) and Short Physical Performance Battery (SPPB) tests. Axial CT images were evaluated at the L3 level using Slice-O-Matic software (Tomovision Quebec, Canada). Superficial adipose tissue(SAT) was calculated from extra-muscular tissue with densities ranging from -190 to -30 Hounsfield Units (HU). Visceral adipose tissue (VAT) was calculated from non-subcutaneous tissue with densities from -150 to -50 HU, with values in cm2. BSA and BMI were calculated using standard formulas. Descriptive statistics(mean and standard deviation (SD)) were estimated and simple linear regression models were used to evaluate associations of comorbidities, function, and clinically-used body metrics and continuous adiposity measures. Pearson correlation coefficients were estimated to assess the relationship between adiposity measures.Results: In a sample of 99 women, mean age was56 (SD 13.1), BMI was 30 (SD 7), 47% were obese (≥30 kg/m2), and mean number of comorbidities was1.3 (SD 1.5).The mean VAT was 113.9 (SD 71.2), 50% had high VAT (>100 cm2), and the mean SAT was 294.2 (SD 71.2). For each additional comorbidity, mean VAT increased by 16.68, and SAT increased by 21.6. Both arthritis and high blood pressure were associated with higher VAT (+67.2 p<.0001 and +67.3 p<.0001, respectively) and higher SAT (+94.3 p=.002 and +104.3 p=.0008, respectively). Peripheral vascular disease and emphysema/chronic bronchitis were associated with higher VAT (+57.7 p=.01 and +100.8 p=.02, respectively), but not higher SAT. Higher VAT was seen for patients with TUG >14 seconds +57.87 (p=.004). For each additional point on the SPPB scale, the mean VAT decreased by 12.14(p=.002). For each additional comorbidity, BSA increased 0.035(p=.004) and BMI increased 1.31(p=.003). Strong positive correlations with VAT were seen for BSA (.697 p<.001), BMI (0.681 p<.001) and SAT (0.636 p<0001), as well as SAT with BSA (0.813 p<.0001) and BMI (.855 p<.0001). Conclusion: Comorbidities, function and commonly-used body metrics (BSA, BMI) are associated with adiposity metrics (VAT, SAT). All of these body composition metrics are associated with measures of function. Citation Format: Gabriel F. P. Aleixo, Allison M Deal, Shlomit S Shachar, Hyman B Muss, Kirsten A Nyrop, Ji Hye Park, Hyeon Yu, Grant R Williams. Adiposity, comorbidities, and function in patients with early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-48.

Abstract P3-08-73: Muscle measures, body composition, and function in patients with early breast cancer

Abstract Introduction: Sarcopenia and muscle composition are associated with treatment-related toxicities and adverse events in women with EBC (Shachar 2017). We investigated the relationship of muscle mass with other measures of body composition as well as comorbidities, physical function, fatigue, and quality of life. Methods: Women age 21 or older were enrolled in intervention studies (NCT02167932, NCT02328313) investigating home-based walking during chemotherapy for early breast cancer (stage I-III). Prior to the start of chemotherapy, patients completed the Short Physical Performance Battery (SPPB) and the Timed Up and Go (TUG) test. When available from staging, transverse views of computed tomography (CT) through L3 lumbar segments were analyzed using Slice-O-Matic software (Tomovision Quebec, Canada) to ascertain skeletal muscle area (SMA= -29 to +150 Hounsfield Units), skeletal muscle density (SMD= average attenuation of skeletal muscle in HU), skeletal muscle index (SMI= SMA/height2), and skeletal muscle gauge (SMG= SMI x SMD). BSA and BMI were calculated using standard formulas. Descriptive statistics (mean and standard deviation (SD)) were estimated and simple linear regression models were used to evaluate associations of body composition, function and quality of life and continuous muscle measures. Pearson correlation coefficients were estimated to assess the relationship between muscle metrics. Results: In 99 patients, mean age was 56 (SD 13), BMI was 30 (SD 7), 47% were obese (≥30 kg/m2), and 54% had stage III breast cancer. Mean SMI was 45.3 (SD. 8.5), 26% were sarcopenic (SMI <40cm2/m2), mean SMD was 31.2 (SD 9.8), 77% had low SMD (HU <37.8), and mean SMG was 1413.8 (SD 71.2) [normal SMG is >1512 Arbitrary Units]. For each additional comorbidity, mean SMD decreased by 1.91 (p=.003), mean BSA increased by 0.035 (p=.02), and mean BMI increased by 1.31 (p=.005). Lower SMD and SMG were seen for patients with TUG >14 seconds (-5.70, p=.04 and -325.4, p=.02, respectively). The mean SMD increased by 1.22 (p=.02) for each additional point on the SPPB scale. For the correlation between BMI and muscle matrices, there was a strong positive correlation for SMI (+0.648 p<.0001) and a moderate negative correlation for SMD (-0.490 p<.0001). Between BSA and muscle matrices, there was a moderate positive correlation for SMI (+0.433 p<.0001), a strong negative correlation for SMD (-0.572 p <.0001), and a low negative correlation for SMG (-0.282 p=.004). Conclusion: Our study showed that sub-optimal muscle metrics, especially lower muscle mass and density, were correlated worse physical function in women with EBC. We also show that muscle metrics are associated with conventional measures of body composition. Citation Format: Gabriel F. P. Aleixo, Allison M Deal, Grant R Williams, Hyman B Muss, Kirsten A Nyrop, Ji Hye Park, Hyeon Yu, Shlomit S Shachar. Muscle measures, body composition, and function in patients with early breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-73.

Abstract P3-08-46: Correlation of prognostic indicators based on clinical and pathological features in hormone receptor positive and HER2 receptor negative early breast cancer with the 21 gene assay recurrence score

Abstract Background: With the advent of genomic testing in routine practice to predict the benefit of adjuvant chemotherapy, in a resource limited health service, many multi-disciplinary breast cancer teams are relying on known clinical and pathological factors to determine which patients undergo testing or to avoid/receive chemotherapy in hormone receptor positive, HER2 negative (HR+, HER2 -ve) breast cancer. These factors are manipulated in formulae or in online prognostic calculators to determine "risk". Oncotype DX Recurrence Score® is routinely used in the UK to determine benefit of adjuvant chemotherapy in early breast cancer according to National guidelines (NICE) which determines risk using the Nottingham Prognostic Index (NPI) and Predict. Methods: With the kind permission of surgical and oncology colleagues within the Wales Cancer Network Breast Clinical Site Group, all patients with HR+, HER2-ve invasive breast cancer who had undergone Oncotype DX Recurrence Score® testing between 31/10/15 and 1/11/18 were matched to the prospectively held national cancer database. Post- operative tumour size, grade, nodal status, age of patient and route of diagnosis were then utilized to calculate the NPI for each case and the PREDICT! on line calculator for chemotherapy benefit in addition to endocrine therapy. A correlation co-efficient was then calculated for NPI, PREDICT 5 and PREDICT 10 to the recurrence score®. Ki 67 is not routinely calculated. Results: There were 734 cases with a RS® available matched to the cancer registry database, 96 of which had missing data items preventing calculation of NPI or PREDICT! values. Demographics of patients tested – n= 734MeanMedianRangeAge (years)585927-97Referral RouteBreast Cancer Screening296GP Referral/ Symptomatic438RS®Low - <18381Intermediate: 18-25202Intermediate: 26-3051High - ≥31100 GradeG143G2457G3225Grade unknown4Tumour Size T1244T2402T346T45Size unknown36Nodal StatusN0528N1mic58N1 (1_3)110Nodal status unknown38 all RS® (n= 638)r co-efficient of correlationNPI0.07Predict 5 year0.09Predict 10 year0.08LN0 (n= 481)NPI0.12Predict 5 year0.11Predict 10 year0.10LN mic (n= 52)NPI0.29Predict 5 year0.40Predict 10 year0.35LN1 (1_3) (n=105)NPI0.02Predict 5 year0.05Predict 10 year0.05 Conclusions: This is the largest cohort analysis in the UK of recurrence score testing published to date and covers a wider range of node negative, micro metastatic and node positive patients. We have demonstrated a weak correlation between the RS® and the NPI or PREDICT outcome in predicting benefit of chemotherapy and we do not believe these clinic-pathological surrogates should be relied upon to determine indications for adjuvant chemotherapy in HR+, HER2-ve early breast cancer patients or in determining if Oncotype DX Recurrence Score® testing should be performed in order to reduce over treatment with chemotherapy. Citation Format: Marianne Dillon, Adam Yarwood, Daniel Thomas, Wales Cancer Network Breast Clinical Steering Group. Correlation of prognostic indicators based on clinical and pathological features in hormone receptor positive and HER2 receptor negative early breast cancer with the 21 gene assay recurrence score [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-08-46.

Hepatitis B Reactivation: A Potentially Serious Complication of Chemotherapy for Solid Tumors

We present a case of hepatitis B reactivation in a patient receiving adjuvant chemotherapy for early breast cancer. This is a 49-year-old post-menopausal, Chinese female with history of chronic hepatitis B with inactive carrier state, and right invasive ductal carcinoma staged as cT2N1M0, pT2N1aM0, anatomic stage IIB, prognostic stage IIA, estrogen and progesterone receptor positive, and human epidermal growth factor 2 negative. The patient underwent bilateral mastectomy with implant reconstruction and right axillary lymph node dissection followed by adjuvant chemotherapy planned as dose dense doxorubicin and cyclophosphamide (ddAC), followed by dose dense paclitaxel (ddT). Two weeks after her first cycle of dose dense paclitaxel, she developed grade III HBV reactivation with hepatitis. This report highlights HBV reactivation as a potential complication of chemotherapy for solid tumors, and reviews recommended HBV screening, prevention and management of HBV reactivation in this patient population.

Congruence of patient- and clinician-reported toxicity in women receiving chemotherapy for early breast cancer

Congruence of patient- and clinician-reported toxicity in women receiving chemotherapy for early breast cancer

Harmonizing gene signatures to predict benefit from adjuvant chemotherapy in early breast cancer.

Breast cancer is a heterogeneous disease, including different subtypes with their own biology, prognosis, clinical characteristics and treatment. To date, traditional clinical and pathological determinants remain the main factors guiding treatment decision-making; however, the development of multigene assays improved the ability to predict the risk of recurrence in patients with early-stage breast cancer. These tools underwent an extensive independent validation and have already been partly incorporated into clinical practice. The current article summarizes current evidence for the use of the different genomic assays in clinical practice, their characteristics and validation studies. A few studies comparing available genomic assays revealed that they provide different information with a modest correlation and that they are not interchangeable; other trials are currently ongoing in this setting. Variability across different gene signatures may be a challenge for the optimal management of the individual patient, hence each assay should be used for the clinical setting in which it has been validated.

Acupuncture for Chemotherapy-Induced Peripheral Neuropathy in Breast Cancer Survivors: A Randomized Controlled Pilot Trial.

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating long-term side effects in breast cancer survivors. We conducted a randomized controlled pilot trial to assess the feasibility, safety, and effects of an acupuncture intervention on CIPN in this population. Women with stage I-III breast cancer with grade 1 or higher CIPN after taxane-containing adjuvant chemotherapy were randomized 1:1 to an immediate acupuncture (IA) arm or to a waitlist control group (CG). Participants in the IA arm received 18 sessions of acupuncture over 8 weeks, then received no additional acupuncture. Patients in the CG arm received usual care over 8 weeks, followed by nine sessions of acupuncture over 8 weeks. Measures including Patient Neurotoxicity Questionnaire (PNQ), Functional Assessment of Cancer Therapy-Neurotoxicity subscale (FACT-NTX), and Brief Pain Inventory-short form (BPI-SF) were collected at baseline and at 4, 8, and 16 weeks after enrollment. Forty women (median age, 54) were enrolled (20 to IA and 20 to CG), with median time between completion of chemotherapy and enrollment of 14 months (range 1-92). At 8 weeks, participants in the IA arm experienced significant improvements in PNQ sensory score (-1.0 ± 0.9 vs. -0.3 ± 0.6; p = .01), FACT-NTX summary score (8.7 ± 8.9 vs. 1.2 ± 5.4; p = .002), and BPI-SF pain severity score (-1.1 ± 1.7 vs. 0.3 ± 1.5; p = .03), compared with those in the CG arm. No serious side effects were observed. Women with CIPN after adjuvant taxane therapy for breast cancer experienced significant improvements in neuropathic symptoms from an 8-week acupuncture treatment regimen. Additional larger studies are needed to confirm these findings. Chemotherapy-induced peripheral neuropathy (CIPN) is a toxicity that often persists for months to years after the completion of adjuvant chemotherapy for early breast cancer. In a randomized pilot trial of 40 breast cancer survivors with CIPN, an 8-week acupuncture intervention (vs. usual care) led to a statistically and clinically significant improvement in subjective sensory symptoms including neuropathic pain and paresthesia. Given the lack of effective therapies and established safety profile of acupuncture, clinicians may consider acupuncture as a treatment option for mild to moderate CIPN in practice.

Neutropenic complications in the PANTHER phase III study of adjuvant tailored dose-dense chemotherapy in early breast cancer

Introduction: Myelosuppresion is a common side effect of chemotherapy and granulocyte-colony stimulating factor (G-CSF) is often used to reduce the risk of neutropenic events. The purpose of this exploratory analysis was to investigate neutropenic complications in the phase III PANTHER trial of standard 3-weekly chemotherapy with 5-fluorouracil, epirubicin and cyclophosphamide plus docetaxel (FEC/D) versus bi-weekly tailored dose-dense EC/D adjuvant chemotherapy in breast cancer.Patients and methods: Febrile neutropenia, neutropenic infection and infection grade 3–4 according to CTC AE 3.0, were explored in relation to G-CSF use. Per cycle analysis was performed concerning dose reduction and dose delays in conjunction with G-CSF administration.Results: In the experimental group, 98.9% of patients received primary G-CSF support during EC and 97.4% during docetaxel, compared with 49.7% during FEC and 63.88% during docetaxel in the standard group. Overall, the use of G-CSF was associated with a lower risk for developing neutropenic events (OR 0.44, 95% CI 0.35–0.55, p < .001). Chemotherapy delays due to neutropenia and leukopenia were significantly decreased among patients that received G-CSF (OR 0.098, 95% CI 0.06–0.15 and OR 0.32, 95% CI 0.18–0.58, respectively).Discussion: In conclusion, G-CSF support reduces neutropenic events and permits increased relative dose intensity, which is essential for improved survival outcomes.

250P - The concordance of treatment decision guided by oncotype and the PREDICT tool in early stage breast cancer

BackgroundDecision on adjuvant chemotherapy for early breast cancer can be guided by genomic assays. PREDICT is a validated free online tool that estimates the benefit from adjuvant chemotherapy using clinical and pathological data. The concordance of expected clinical decisions guided by Oncotype analysis and the PREDICT in unknown. MethodsA retrospective single center cohort study comprising all women with estrogen receptor (ER) positive, human epidermal growth factor receptor 2 negative, node negative disease, whose tumors were sent for OncotypeDX analysis. Estimation of 10-year overall survival (OS) benefit from 2nd generation chemotherapy was calculated using the PREDICT 2.1v tool. Omission of chemotherapy was expected to be advised when Oncotype recurrence score (RS) was ≤25 or when the estimated 10-year OS benefit by the PREDICT was <2%. The tests were considered concordant for women with RS≤25 and estimated PREDICT benefit<2% or for women with RS>25 and estimated PREDICT benefit ≥2%. Concordance was presented using percentages and the K coefficient. The impact on concordance of pre-specified histological features was assessed, including tumor size, intensity of ER and progesterone receptor (PR), grade, Ki67 and perineural and lymphovascular invasion. The difference between the subgroups was calculated using Chi-squared test. ResultsA total of 445 women were included. Overall concordance was 75% (K=0.284), with 55 (12.5%) women with low RS but estimated PREDICT benefit ≥2% and 55 (12.5%) with high RS and estimated PREDICT benefit<2%. The concordance was significantly higher for grade 1 disease compared to grade 2-3 (93% vs 72%, p<0.001), tumor ≤1cm compared to>1cm (85% vs 72%, p=0.009), PR positive compared to PR negative (78% vs 58%, p<0.001) and ki67<20% compared to≥20% (82% vs 54%, p<0.001). The intensity of ER and the presence of perineural or lymphovascular invasion had no significant impact on concordance. ConclusionsCompared to PREDICT, using Oncotype in node negative, ER positive disease is expected to change clinical decision in a quarter of patients. The concordance is influenced by pathological features. The use of Oncotype may not be necessary for clinically very low risk patients. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureH. Goldvaser: Honoraria (self): Roche. R. Yerushalmi: Honoraria (self): Roche; Honoraria (self): Medison; Honoraria (self): AstraZeneca; Honoraria (self): Novartis; Honoraria (self): Teva. M. Sarfaty: Honoraria (self): Roche; Honoraria (self): MSD; Honoraria (self): Medison; Honoraria (self): Novartis. All other authors have declared no conflicts of interest.

Recent Development of Treatment Strategy for Early Breast Cancer

Abstract Strategy of peri-operative chemotherapy for early breast cancer has been changed dramatically during these 10 years. Development of high efficacy regimen with strong cell-killing drugs for reducing the recurrence risk was first priority in our research in the beginning (escalation). After that, selection of proper strength regimen adapting to recurrence risk expectation of each patient was coming to the main stream (de-escalation). As a most recent topic, response guide treatment with neo-adjuvant therapy contributes dramatically for drug development, in which patients with non-pathological response to initial therapy thought to be a proper candidate for additional adjuvant therapy with investigation new drug. In this lecture I would like to summarize the recent changes of treatment strategy for early breast cancer.

209P - Influence of age on the indication of adjuvant chemotherapy in early breast cancer using Oncotype DX. An analysis of 240 patients treated in the Institut Catala d’Oncologia (ICO) hospitals

BackgroundBenefit derived from adjuvant chemotherapy (CT) is doubtful in a high percentage of patients (pt) with hormone-receptor–positive HER2 negative early breast cancer. The 21-gene recurrence-score (RS) assay Oncotype DX, provide prognostic and predictive information. Results of the TAYLORx study have confirmed that most of patients with negative node status and RS>25 can avoid CT without increasing their risk of relapse. However, pt<50 years (y) and RS>20 showed benefit with CT. MethodsAim: To analyse the impact of age using RS test to change the indication of adjuvant CT and the relationship between different clinical pathological factors and the RS value. We analysed 240 cases out of 251 RS test performed in the 3 ICO Centers during 2017-2018. We compared the adjuvant treatment initially planned according to institutional protocol with the treatment given after RS in the total cohort and in pt<50 y. We performed a logistical regression analysis of pathological factors and RS. ResultsCT was indicated in all pt before knowing the RS results. Only 46pt (19%) received CT after RS results. 14 out of 88pt < 50 y received adjuvant CT (15%). 15pt <50 y had a RS between 21-25, only 5 of them received CT, because in most of them, the RS was performed prior TAILORx results were published. Nowadays, all of these 15pt would had received CT: 61/240 (25%). Clinical-pathological characteristics of the series are summarized in the Table. Of the risk factors analysed, only Ki67>25 (<0.001) and PR≤20% (0.01) showed a statistically significant relationship with a higher probability of RS>25 in a multivariate analysis.Table209PTableAge median (range)53 (19-76) <50 y 35.1% ≥50 y 64.9%Tumor size median15mmHistological gradeG1 23% G2 69.7% G3 4.4%Progesterone receptor≤20% 21% >20% 78%Ki67 median (p25-75)20 (13,28) ≤14 27% 14-25 41% >25% 31%Nodal statuspN0 57%pN1mic 15%pN1a 27% Conclusions82% of pt of our series could avoid CT, however this proportion change after TAYLORx results in younger patients. Today 75% of these pt would had avoided CT. Ki67 > 25% and Progesterone Receptor ≤20% were the only pathological factors associated with an increased risk of RS>25. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

278P - Correlation between radiologic complete response (rCR) in contrast-enhanced magnetic resonance imaging (CE-MRI) after neoadjuvant chemotherapy for early breast cancer and pathologic complete response and their impact in recurrence-free survival

BackgroundPatients with early breast cancer (EBC) achieving pathologic complete response (pCR) after neoadjuvant chemotherapy (NACT) have a favorable prognosis. Breast surgery and more chemotherapy treatment might be avoided in patients in whom the presence of residual tumor can be ruled out with high confidence. We investigated the diagnostic accuracy of contrast enhanced MRI (CE-MRI) in predicting pCR and long-term outcome after NACT. MethodsPatients with EBC, who had undergone CE-MRI before and after NACT, were retrospectively analyzed (n=421), and regarding to the absence (radiologic complete remission; rCR) or presence (no-rCR) of residual contrast enhancement. ResultsOverall rCR and pCR rates were 35% (147/421) and 36% (154/421), respectively. We found a total of 70% (101/144) of rCR corresponded to a pCR (meaning the positive predictive value - PPV). In contrast, in 80% (219/272) of patients, residual tumor observed on MRI was pathologically confirmed (meaning the negative predictive value - NPV). Sensitivity to detect a pCR was 65% (101/154), while specificity to detect residual tumor and accuracy were 83% (219/262); and 76% (320/421), respectively. The PPV was significantly lower in luminal compared to HER2 positive and triple negative tumors (10/34 = 29 % vs. 50/62 = 81% and 41/48 = 85% respectively). The concordance between rCR and pCR was moderate (Cohen’s kappa − 0.5) but with low level in luminal tumors (Coheńs Kappa – 0.3). In multivariate analysis both assessments were significantly associated with disease free survival (rCR : HR:0,344 P=0.001; pCR : HR : 0,154 P=0.000), but not in luminal tumors (rCR : HR:0,813 P=0.692; pCR : HR : 0,326 P=0.275). ConclusionsThe accuracy of preoperative CE-MRI to predict pCR after NACT for EBC is moderate but in luminal tumors did not accurately predict pCR. However, rCR was strongly associated with favorable RFS, especially in HER2 positive and triple negative breast cancer tumors. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

266P - Pathologic response and survival efficacy in patients with initial nodal involvement after neoadjuvant chemotherapy in early breast cancer

BackgroundNodal involvement is a common prognostic factor in early breast cancer (EBC) but their response and assessment after neoadjuvant chemotherapy (NAC) is controversial, hence its impact in survival is not clear. MethodsWe analyze a cohort of 308 EBC patients with initial nodal involvement and their response to neoadjuvant chemotherapy and their impact in disease free survival (DFS). ResultsMedian age was 52 (range 29-87), median tumor size was 38mm (10-100) and 178 patients (57,8%) had initial palpable node involvement. According to the immunohistochemical expression of hormonal receptors, Ki 67 and HER2; 110 patients (35,7%) was HER2 positive, 119 (38,6%) luminal and 79 (25,6%) triple negative breast cancer. After NAC we found a total of pathological complete response in breast (pCRb) of 30% and pathological complete response in axilla (pCRa) of 45%. Response by different subtypes was: in HER2 a pCRb 41,8% and pCRa 56,3%; luminal a pCRb 13% pCRa 30,3% and triple negative a pCRb 41,8% pCRa 50,6%. Luminal patients achieved the worst axillary response (p:0,004) and without other variables with significant association like tumor initial size or palpable axillary nodes. The global coincidence between pCRb and pCRa was 83% and very similar in the different subtypes. Axillary pCR was associated with a better DFS in the global series (HR: 0,377 p:0,000) but not in the luminal patients (HR:0,455 p:0,072) and the median survival in patients with pCRa was 157 months in contrast to 121 in patients that not achieve a pCRa (153 vs 99 in HER2, 160 vs 141 in luminal and 167 vs 93 in triple negative). ConclusionsThe complete pathological response in axila after neoadjuvant chemotherapy is 45% in our serie but lower in luminal patients with only a 30%. There was a high level of concordance between pCR in breast and axilla in all subtypes with an 83%. Achieving pCR in axilla is associated with better disease free survival but this benefit is lower in luminal phenotype. Legal entity responsible for the studyThe authors. FundingHas not received any funding. DisclosureAll authors have declared no conflicts of interest.

Zwischen Präzisionsmedizin und symbolischer Bewältigung: Was Ärzte wünschen

IntroductionCaring for patients is inevitably fraught with uncertainties. These may result from clinicians not having or not using the available knowledge, from the incompleteness of the medical science base as a whole, or from the inevitable randomness of biological, psychological and social phenomena. Advances in science promise to reduce uncertainty by making ever more precise diagnosis and treatment possible. MethodsHere, we discuss two typical examples of scientific progress and on how they impact on clinical uncertainty: first, the stratification of chemotherapy for early breast cancer by a 70-gene signature, and second, the interpretation of knee MRI regarding meniscal damage. ResultsAccording to a large randomized trial, the 70-gene -signature successfully differentiates between strata for invasive treatments. The quantitative results and related trade-offs, however, pose considerable difficulties for patient information and shared decision-making, thus increasing uncertainty. Knee complaints are only weakly associated with MRI findings. Pathological findings are highly prevalent in symptom-free individuals. ConclusionRecent advances in diagnostic methods increase the cognitive demands on clinicians and thus their uncertainty. By uncritically using advanced technologies in their practice, physicians exploit their archetypical healing powers. In a paradoxical way, modern technologies reduce uncertainties felt by doctors and their patients in an archaic fashion.

Risk of emergency hospitalisation and survival outcomes following adjuvant chemotherapy for early breast cancer in New South Wales, Australia.

To examine risk of emergency hospital admission and survival following adjuvant chemotherapy for early breast cancer. Linked data from New South Wales population-based and clinical cancer registries (2008-2012), hospital admissions, official death records and pharmaceutical benefit claims. Women aged ≥18years receiving adjuvant chemotherapy for early-stage operable breast cancer in NSW public hospitals were included. Odds ratios (OR) for emergency hospitalisation within 6months following chemotherapy initiation were estimated using logistic regression and survival using Kaplan-Meier and Cox proportional hazards methods. A total of 3,950 women were included and 30.6% were hospitalised. The most common principal diagnosis at admission was neutropenia (30.8%). Women receiving docetaxel/carboplatin/trastuzumab (TCH) and docetaxel/cyclophosphamide (TC) were the most frequently hospitalised. After adjustment for demographic and clinical factors, the increased risk of hospitalisation for TCH and TC remained compared with doxorubicin/cyclophosphamide 3-weekly (OR 1.71, 95% confidence interval [CI] 1.24-2.37 and OR 1.47, 95% CI 1.17-1.85 respectively). Five-year overall survival was similar for women who were (92.2%, 95% CI 90.7-93.8) and were not hospitalised (93.1%, 95% CI 92.1-94.1). Emergency hospitalisations following chemotherapy for early breast cancer were relatively common, especially following docetaxel-containing protocols. Further examination of reasons for admission is needed to inform actions to improve patient safety.

Axillary Surgery Following Neoadjuvant Chemotherapy – Multidisciplinary Guidance From the Association of Breast Surgery, Faculty of Clinical Oncology of the Royal College of Radiologists, UK Breast Cancer Group, National Coordinating Committee for Breast Pathology and British Society of Breast Radiology

AimsThese multidisciplinary guidelines aim to provide clinically helpful, evidence-based recommendations on the surgical management of the axilla in patients who have received neo-adjuvant chemotherapy for early breast cancer. Materials & methodsFollowing a review of published evidence, a writing group representing all disciplines quorate within a breast cancer multidisciplinary meeting prepared the guidelines. Key recommendationsIn patients presenting with clinically node negative axillae, sentinel node biopsy (SNB) may be performed prior to or on completion of neo-adjuvant chemotherapy (NACT). In patients presenting with clinically node positive axillae, SNB may be safely considered following completion of NACT. Four nodes should be removed with dual mapping. If evidence of complete pathological response of previous metastases is seen, axillary radiotherapy may be offered. If residual cancer (isolated tumour cells, micro- or macrometastes) is seen within the SNB, offer axillary node dissection.

A Closed-loop Audit of 5 versus 10 Days of Primary GCSF Prophylaxis to Reduce the Incidence of Febrile Neutropenia in Early Breast Cancer Treatment

Purpose: Current guidelines recommend that patients with early breast cancer receiving chemotherapy that confers >20% risk of febrile neutropenia should have primary prophylactic granulocyte colony-stimulating factor (GCSF) on days 2–6 of chemotherapy [1,2]. An initial audit [3] demonstrated non-inferiority of 5 days versus 10 days of primary prophylactic GCSF in respect of febrile neutropenia rates seen in early breast cancer chemotherapy. Since 1 August 2016, our centre has switched from 10 days of prophylactic GCSF to 5 days. We re-audited febrile neutropenia rates following our change in practice.

Adjuvant trastuzumab chemotherapy in early breast cancer: meta-analysis of randomised trials and cost-effectiveness analysis.

Trastuzumab has a large financial impact on the average cost of breast cancer treatment. This study reassessed the cost-effectiveness of listing the drug on the subsidised Australian Pharmaceutical Benefits Scheme. Using a continuous-time, discrete-event microsimulation model, we examined the effect of 1-year trastuzumab on the total number of disability-adjusted life-years (DALYs) averted among Australian women with human epidermal growth factor receptor-2 (HER2) positive early breast cancer. Target population was women aged 30&ndash;100 years and newly diagnosed with the disease in 2003. The model adjusted for tumour size and followed the women up until death or age 100 years. Uncertainty was examined in univariate and probabilistic multivariate sensitivity analyses. The incremental cost-effectiveness ratio (ICER) was A$132,537 (95% confidence interval 91,172&ndash;200,485) per DALY averted. Results were sensitive to restriction of trastuzumab to high-risk (large tumour) and/or high-benefit (young) patients. Suitable combinations of tumour size and age restrictions would improve the cost-effectiveness of trastuzumab. Specifically, restricting trastuzumab to women aged 40 years or younger with tumour sizes 40+ mm reduced the ICER to A$35,290 per DALY averted. Trastuzumab for HER2-positive early breast cancer had a high ICER. It is unclear why the Pharmaceutical Benefits Scheme listing does not use restrictions to improve the cost-effectiveness of the drug.