Trends in complementary/alternative medicine use by breast cancer survivors: Comparing survey data from 1998 and 2005

BACKGROUND: Use of complementary and alternative medicine (CAM) by women with breast cancer is often said to be increasing, yet few data exist to confirm this commonly held belief. The purpose of this paper is to compare overall patterns of CAM use, as well as use of specific products and therapies at two different points in time (1998 vs 2005) by women diagnosed with breast cancer. METHODS: Surveys were mailed to women randomly selected from the Ontario Cancer Registry (Canada) in the spring of 1998 (n = 557) and again in the spring of 2005(n = 877). RESULTS: The response rates were 76.3% in 1998 and 63% in 2005. In 1998, 66.7% of women reported using either a CAM product/therapy or seeing a CAM therapist at some time in their lives as compared with 81.9% in 2005 (p = 0.0002). Increases were seen in both use of CAM products/therapies (62% in 1998 vs. 70.6% in 2005) and visits to CAM practitioners (39.4% of respondents in 1998 vs 57.4% of respondents in 2005). Women in 2005 reported that 41% used CAM for treating their breast cancer. The most commonly used products and practitioners for treating breast cancer as reported in 2005 were green tea, vitamin E, flaxseed, vitamin C, massage therapists and dietitians/nutritionists. CONCLUSION: CAM use (both self-medication with products and visits to CAM practitioners) increased significantly from 1998 to 2005. Now that more than 80% of all women with breast cancer report using CAM (41% in a specific attempt to management their breast cancer), CAM use can no longer be regarded as an "alternative" or unusual approach to managing breast cancer

The impact of patient characteristics and lifestyle factors on the risk of an ipsilateral event after a primary DCIS: a systematic review

ObjectiveThe ma­jor­ity of ‘low-risk’ (grade I/​II) Duc­tal Car­ci­noma In Situ (DCIS) may not progress to in­va­sive breast can­cer dur­ing a wom­en's life­time. There­fore, the safety of ac­tive sur­veil­lance ver­sus stan­dard sur­gi­cal treat­ment for DCIS is prospec­tively be­ing eval­u­ated in clin­i­cal tri­als. If proven safe and se­lec­tively im­ple­mented in clin­i­cal prac­tice, a sig­nif­i­cant group of women with low-risk DCIS may forego surgery and ra­dio­ther­apy in the fu­ture. Iden­ti­fi­ca­tion of mod­i­fi­able and non-mod­i­fi­able risk fac­tors as­so­ci­ated with prog­no­sis af­ter a pri­mary DCIS would also en­hance our care of women with low-risk DCIS.MethodsTo iden­tify mod­i­fi­able and non-mod­i­fi­able risk fac­tors for sub­se­quent breast events af­ter DCIS, we per­formed a sys­tem­atic lit­er­a­ture search in PUBMED, EM­BASE and Sco­pus.ResultsSix out of the 3870 ar­ti­cles re­trieved were in­cluded for fi­nal data ex­trac­tion. These six stud­ies in­cluded a to­tal of 4950 pa­tients with pri­mary DCIS and 640 recorded sub­se­quent breast events. There was mod­er­ate ev­i­dence for an as­so­ci­a­tion of a fam­ily his­tory of breast can­cer, pre­menopausal sta­tus, high BMI, and high breast den­sity with a sub­se­quent breast can­cer or fur­ther DCIS.ConclusionThere is a lim­ited num­ber of re­cent stud­ies pub­lished on the im­pact of mod­i­fi­able and non-mod­i­fi­able risk fac­tors on sub­se­quent events af­ter DCIS. The avail­able ev­i­dence is in­suf­fi­cient to iden­tify po­ten­tial tar­gets for risk re­duc­tion strate­gies, re­flect­ing the rel­a­tively small num­bers and the lack of long-term fol­low-up in DCIS, a low-event con­di­tion.</p

Association of DCIS Size and Margin Status With Risk of Developing Breast Cancer Post-Treatment: Multinational, Pooled Cohort Study

OBJECTIVE: To examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage and subtype of ipsilateral invasive breast cancer. DESIGN: Multinational, pooled cohort study. SETTING: Four large international cohorts. PARTICIPANTS: Patient level data on 47 695 women with a diagnosis of pure, primary DCIS between 1999 and 2017 in the Netherlands, UK, and US who underwent surgery, either breast conserving or mastectomy, often followed by radiotherapy or endocrine treatment, or both. MAIN OUTCOME MEASURES: The main outcomes were 10 year cumulative incidence of ipsilateral invasive breast cancer and ipsilateral DCIS estimated in relation to DCIS size and margin status, and adjusted hazard ratios and 95% confidence intervals, estimated using multivariable Cox proportional hazards analyses with multiple imputed data RESULTS: The 10 year cumulative incidence of ipsilateral invasive breast cancer was 3.2%. In women who underwent breast conserving surgery with or without radiotherapy, only adjusted risks for ipsilateral DCIS were significantly increased for larger DCIS (20-49 mm) compared with DCIS(hazard ratio 1.38, 95% confidence interval 1.11 to 1.72). Risks for both ipsilateral invasive breast cancer and ipsilateral DCIS were significantly higher with involved compared with clear margins (invasive breast cancer 1.40, 1.07 to 1.83; DCIS 1.39, 1.04 to 1.87). Use of adjuvant endocrine treatment was not significantly associated with a lower risk of ipsilateral invasive breast cancer compared to treatment with breast conserving surgery only (0.86, 0.62 to 1.21). In women who received breast conserving treatment with or without radiotherapy, higher DCIS grade was not significantly associated with ipsilateral invasive breast cancer, only with a higher risk of ipsilateral DCIS (grade 1: 1.42, 1.08 to 1.87; grade 3: 2.17, 1.66 to 2.83). Higher age at diagnosis was associated with lower risk (per year) of ipsilateral DCIS (0.98, 0.97 to 0.99) but not ipsilateral invasive breast cancer (1.00, 0.99 to 1.00). Women with large DCIS (≥50 mm) more often developed stage III and IV ipsilateral invasive breast cancer compared to women with DCISfound. CONCLUSIONS: The association of DCIS size and margin status with ipsilateral invasive breast cancer and ipsilateral DCIS was small. When these two factors were added to other known risk factors in multivariable models, clinicopathological risk factors alone were found to be limited in discriminating between low and high risk DCIS

CALGB 40603 (Alliance): Long-Term Outcomes and Genomic Correlates of Response and Survival After Neoadjuvant Chemotherapy With or Without Carboplatin and Bevacizumab in Triple-Negative Breast Cancer

PURPOSECALGB 40603 (NCT00861705), a 2 × 2 randomized phase II trial, demonstrated that adding carboplatin or bevacizumab to weekly paclitaxel (wP) followed by doxorubicin and cyclophosphamide significantly increased the pathologic complete response (pCR) rate in stage II-III triple-negative breast cancer. We now report long-term outcomes (LTOs) and correlative science end points.PATIENTS AND METHODSThe Kaplan-Meier method was used to estimate LTOs in 443 patients who initiated study treatment. Log-rank tests and Cox proportional hazards models evaluated the impact of clinical characteristics, pathologic response, calculated residual cancer burden (RCB) in patients with residual disease (RD), treatment assignment, and dose delivery during wP on LTOs, including event-free survival (EFS). Genomic predictors of treatment response and outcomes were assessed on pretreatment tumor samples by mRNA sequencing.RESULTSAmong baseline characteristics, only the clinical stage was associated with LTOs. At a median follow-up of 7.9 years, LTOs were not significantly improved with either carboplatin or bevacizumab, overall or in patients with basal-like subtype cancers by genomic analysis. Patients with pCR (n = 205, 46.3%) had significantly higher 5-year EFS (85.5% v 56.6%, log-rank P <.0001) and overall survival (87.9% v 63.4%, P <.0001) rates compared with patients with RD, even those with RCB class I. Among clinical and genomic features, evidence of immune activation, including tumor-infiltrating lymphocytes and low B-cell receptor evenness, was associated with pCR and improved EFS.CONCLUSIONDespite higher pCR rates, neither carboplatin nor bevacizumab appeared to improve LTOs although the study was not powered to assess these secondary end points. pCR was associated with superior LTOs even when compared with minimal RD. Markers of immune activation in pretreatment tumor biopsies were independently associated with higher pCR rates and improved survival

Mechanisms that clear mutations drive field cancerization in mammary tissue

Oncogenic mutations are abundant in the tissues of healthy individuals, but rarely form tumours1–3. Yet, the underlying protection mechanisms are largely unknown. To resolve these mechanisms in mouse mammary tissue, we use lineage tracing to map the fate of wild-type and Brca1−/−;Trp53−/− cells, and find that both follow a similar pattern of loss and spread within ducts. Clonal analysis reveals that ducts consist of small repetitive units of self-renewing cells that give rise to short-lived descendants. This offers a first layer of protection as any descendants, including oncogenic mutant cells, are constantly lost, thereby limiting the spread of mutations to a single stem cell-descendant unit. Local tissue remodelling during consecutive oestrous cycles leads to the cooperative and stochastic loss and replacement of self-renewing cells. This process provides a second layer of protection, leading to the elimination of most mutant clones while enabling the minority that by chance survive to expand beyond the stem cell-descendant unit. This leads to fields of mutant cells spanning large parts of the epithelial network, predisposing it for transformation. Eventually, clone expansion becomes restrained by the geometry of the ducts, providing a third layer of protection. Together, these mechanisms act to eliminate most cells that acquire somatic mutations at the expense of driving the accelerated expansion of a minority of cells, which can colonize large areas, leading to field cancerization

Microcalcification crystallography as a potential marker of DCIS recurrence

Ductal carcinoma in-situ (DCIS) accounts for 20-25% of all new breast cancer diagnoses. DCIS has an uncertain risk of progression to invasive breast cancer and a lack of predictive biomarkers may result in relatively high levels (~ 75%) of overtreatment. To identify unique prognostic biomarkers of invasive progression, crystallographic and chemical features of DCIS microcalcifications have been explored. Samples from patients with at least 5-years of follow up and no known recurrence (174 calcifications in 67 patients) or ipsilateral invasive breast cancer recurrence (179 microcalcifications in 57 patients) were studied. Significant differences were noted between the two groups including whitlockite relative mass, hydroxyapatite and whitlockite crystal maturity and, elementally, sodium to calcium ion ratio. A preliminary predictive model for DCIS to invasive cancer progression was developed from these parameters with an AUC of 0.797. These results provide insights into the differing DCIS tissue microenvironments, and how these impact microcalcification formation. [Abstract copyright: © 2023. The Author(s).

Abstract S2-05: Event-free and overall survival following neoadjuvant weekly paclitaxel and dose-dense AC +/- carboplatin and/or bevacizumab in triple-negative breast cancer: outcomes from CALGB 40603 (Alliance)

BACKGROUND: CALGB (Alliance) 40603 measured the effects of adding carboplatin (Cb) and/or bevacizumab (Bev) to standard neoadjuvant chemotherapy (weekly paclitaxel x 12 then doxorubicin/cyclophosphamide every 2 weeks x 4) on pathologic complete response (pCR) rates in stage II-III triple-negative breast cancer (TNBC). As previously reported (Sikov et al, JCO 2015), pCR breast (ypT0/is) and pCR breast/axilla (pCR Br/Ax) (ypT0/isN0) rates increased from 46% to 60% and 41% to 54%, respectively, with Cb and from 48% to 59% and 44% to 52%, respectively, with Bev. Secondary endpoints included event-free survival (EFS) and overall survival (OS). METHODS: EFS is measured from study entry to ipsilateral invasive breast or locoregional recurrence, distant recurrence or death from any cause and OS from study entry to death from any cause in all patients (pts) who started study treatment. Pts without an event were censored as of their last clinical assessment. Hazard ratios (HR) were calculated for pts who achieved pCR vs. not and for pts assigned to receive drug (Cb or Bev) vs. not. All p-values are 2-sided. RESULTS: 443 pts started study treatment. Median follow-up was 39 months (range 28-66). 110 EFS events and 77 deaths have been reported. At 3 yrs, overall EFS was 74.1% and OS 83.2%. Pts who achieved pCR breast had 3-yr EFS of 84.8% vs. 61.8% for those who did not. Table 1 shows the association between pCR and pCR or minimal residual invasive disease (Residual Cancer Burden Class I (RCB I), Symmans et al, JCO 2007) and outcomes; p-values for all comparisons \u3c0.0001: Table 1 pCR Breast pCR Br/Ax pCR Br/Ax or RCB I Yes/No N (%) 231 (52%)/212 (48%) 207 (47%)/236 (53%) 266 (60%)/177 (40%) EFS-HR 0.33 (0.22-0.50) 0.30 (0.19-0.46) 0.29 (0.20-0.43) OS-HR 0.28 (0.17-0.46) 0.20 (0.11-0.36) 0.21 (0.13-0.34) Pts assigned to Cb vs. not had 3-yr EFS 76.5% vs. 71.6% and OS 81.9% vs. 84.6%. Pts assigned to Bev vs. not had 3-yr EFS 75.5% vs. 72.9% and OS 85.5% vs. 80.9%. Table 2 shows HRs by assigned treatment: Table 2 Cb Bev N (Yes/No) 225/218 222/221 EFS - HR 0.84 (0.58-1.22) p=0.36 0.80 (0.55-1.17) p=0.25 OS - HR 1.15 (0.74-1.79) p=0.53 0.76 (0.49-1.19) p=0.23 CONCLUSIONS: Pts with TNBC who achieved pCR with study treatment had significantly better EFS and OS than pts who did not, consistent with findings from a published meta-analysis (Cortazar et al, Lancet 2014); the addition of RCB I did not weaken this association. Our study was not powered to assess the impact of Cb or Bev on these endpoints. While our findings are consistent with predictions from the meta-analysis as to the impact of raising the pCR rate on EFS (Berry-Hudis, JAMA Oncology 2015), the wide confidence intervals illustrate the challenge of conclusively demonstrating a correlation between pCR increment and EFS benefit, especially as the control pCR rate rises. While the addition of Bev has failed to improve long-term outcomes in TNBC in large randomized adjuvant trials, our results support ongoing and planned neoadjuvant and adjuvant studies designed to further assess the value of Cb-containing regimens in stage II-III TNBC. Support: U10s - CA180821, CA180882, CA180820, CA076001, CA025224, CA180868, CA180888

FNIRS BRAIN IMAGING IS CAPABLE OF DISCERNING HEMISPHERIC LATERALITY DURING LOWER-BODY CONTRACTIONS

Rob MacLennan1, Jesus Hernandez-Sarabia2, Shawn Reese1, Jocarol Shields1, Claire Smith1, Katharina Stute3, Jordyn Collyar1, Alex Olmos1, Tyler Danielson1, Demi MacLennan4, Jason Pagan5, Ryan Girts6, Kylie Harmon7, Nicholas Coker8, Joshua Carr9, Xin Ye10, Jonathan Perry11, Matt Stock5 and Jason DeFreitas1 1Oklahoma State University, Stillwater, OK 2California State University – Bakersfield, Bakersfield, CA 3Chemnitz University of Technology, Chemnitz, Germany 4The Ohio State University, Columbus, OH 5University of Central Florida, Orlando, FL 6Pfeiffer University, Misenheimer, NC 7Syracuse University, Syracuse NJ 8Springfield College, Springfield, MA 9Texas Christian University, Fort Worth, TX 10University of Hartford, West Hartford, CT 11Houston, TX BACKGROUND: Use of functional near-infrared spectroscopy (fNIRS) to measure and image brain activity during movement is increasing. This technique uses near-infrared light to detect changes in oxygenation in the cortex which are associated with increased cortical activity. However, fNIRS is known to have lower spatial resolution than other brain imaging techniques. Due to its relatively low spatial resolution, it is unclear if fNIRS can discriminate between nearby areas of the motor cortex (M1). This capability is particularly important in studies requiring lower extremity contractions for 2 reasons: 1.) the left and right leg areas of the motor cortex are in close proximity, with only the longitudinal fissure separating them, and 2.) the cortical areas responsible for the most distal musculature descend inferiorly into the fissure, and are therefore deeper than most motor areas. PURPOSE: To determine fNIRS’ ability to discern laterality of isolated unilateral lower body contractions. METHODS: Thirty-five young volunteers visited the lab one time. Subjects wore a cap with an optical source over the intersection of the central sulcus and the longitudinal fissure and 2 optical detectors positioned 3 cm laterally in both directions over the left and right motor cortices. Brain activity was recorded while subjects performed sustained 15-second contractions with their right and left legs against an isometric dynamometer at 30% of their maximal force. The mean hemodynamic responses were analyzed with a 2-way (contraction type [left & right legs] × hemisphere [left & right detectors]) repeated measures ANOVA. RESULTS: There was a significant contraction type × hemisphere interaction (p = 0.002). During right leg contractions, activity in the left hemisphere was 77% higher than activity in the right hemisphere. During left leg contractions, activity in the right hemisphere was 43% higher than activity in the left hemisphere. CONCLUSION: The significant interaction found in this study suggests that fNIRS is capable of discerning nearby areas of the motor cortex. Further, this technology has sufficient depth of penetration and spatial resolution to identify which cortical hemisphere is active during a unilateral lower body contraction