Black–white differences in receipt and completion of adjuvant chemotherapy among breast cancer patients in a rural region of the US

Recent breast cancer treatment studies conducted in large urban settings have reported racial disparities in the appropriate use of adjuvant chemotherapy. This article presents the first focused evaluation of black–white differences in receipt and completion of chemotherapy for breast cancer in a primarily rural region of the United States. We performed chart abstraction on initial therapy received by 868 women diagnosed with Stages I, IIA, IIB, or IIIA breast cancer in 2001–2003 in southwest Georgia (SWGA). For chemotherapy, information collected included treatment plan, dates of delivery, concordance between therapy planned and received, and date and reasons for end of treatment. The patient’s age at diagnosis, race, marital status, insurance coverage, hormone receptor status, comorbidities, socioeconomic status, urban/rural status, treatment site, and distance to the site were also collected. Following univariate analyses, we used multivariable logistic regression modeling to examine the impact of race on the likelihood of (1) receiving chemotherapy and (2) completing planned chemotherapy. For patients terminating chemotherapy prematurely, the reasons were documented. The results showed that the unadjusted black–white difference in receipt of chemotherapy (48.3 vs. 36.0%) was significant, but in the multivariable analysis the black–white odds ratio (OR = 1.18) was not. While the unadjusted black–white difference (92.0 vs. 87.8%) in completing chemotherapy was not significant, in multivariable models black race was positively associated with completing care (p ranging from 0.032 to 0.087 and OR, correspondingly, from 2.16 to 2.64). The impact of race on completing chemotherapy was influenced by marital status, with a significant black–white difference for patients not married (OR = 4.67), but no difference for those married (OR = 1.06). We find compelling racial differences in this largely rural region—with black breast cancer patients receiving or completing chemotherapy at rates that equal or exceed white patients. Further investigation is warranted, both in SWGA and in other rural regions.     

Is cognitive dysfunction a complication of adjuvant chemotherapy in the older patient with breast cancer?

For a number of years, patients have anecdotally reported changes in memory and concentration problems after receiving chemotherapy for breast cancer. Neuropsychological studies have been performed to seek objective evidence as to the existence and extent of this phenomenon; however, these studies were primarily performed in younger women and there is sparse data regarding the impact of adjuvant chemotherapy on an older woman’s cognition. The objective of this paper was to evaluate the current literature in order to propose ways to overcome methodological limitations of studies to consider whether chemotherapy-associated cognitive dysfunction exists in older patients and if so, who is at risk. A systematic review of relevant literature was performed including study design, mean age of participants, treatment received, neuropsychological tests employed, timing of assessments, definition of cognitive impairment, and results. The literature primarily consists of small studies, which lack a prospective longitudinal design, vary in design measures, and exclude older patients who are at greatest risk for cognitive impairment. Since aging is the number one risk factor for breast cancer, future studies of the neuropsychological impact of chemotherapy should include older patients.     

Cost–utility of adjuvant zoledronic acid in patients with breast cancer and low estrogen levels

Background

Adjuvant zoledronic acid (za) appears to improve disease-free survival (dfs) in women with early-stage breast cancer and low levels of estrogen (lle) because of induced or natural menopause. Characterizing the cost–utility (cu) of this therapy could help to determine its role in clinical practice.

Methods

Using the perspective of the Canadian health care system, we examined the cu of adjuvant endocrine therapy with or without za in women with early-stage endocrine-sensitive breast cancer and lle. A Markov model was used to compute the cumulative costs in Canadian dollars and the quality-adjusted life-years (qalys) gained from each adjuvant strategy, discounted at a rate of 5% annually. The model incorporated the dfs and fracture benefits of adjuvant za. Probabilistic and one-way sensitivity analyses were conducted to examine key model parameters.

Results

Compared with a no-za strategy, adjuvant za in the induced and natural menopause groups was associated with, respectively, $7,825 and $7,789 in incremental costs and 0.46 and 0.34 in qaly gains for cu ratios of $17,007 and $23,093 per qaly gained. In one-way sensitivity analyses, the results were most sensitive to changes in the za dfs benefit. Probabilistic sensitivity analysis suggested a 100% probability of adjuvant za being a cost-effective strategy at a threshold of $100,000 per qaly gained.

Conclusions

Based on available data, adjuvant za appears to be a cost-effective strategy in women with endocrine-sensitive breast cancer and lle, having cu ratios well below accepted thresholds.     

Phase 2 study of adjuvant chemotherapy with docetaxel,capecitabine, and cisplatin in patients with curatively resected stage IIIB–IV gastric cancer

Gastric Cancer - Postoperative chemotherapy with S-1 or capecitabine plus oxaliplatin is a standard treatment for resectable gastric cancer (GC). However, survival outcomes of stage IIIB–IV...     

The prognostic value of the tumor–stroma ratio is most discriminative in patients with grade III or triple-negative breast cancer

The tumor–stroma ratio (TSR) was evaluated as a promising parameter for breast cancer prognostication in clinically relevant subgroups of patients. The TSR was assessed on hematoxylin and eosin-stained tissue slides of 1,794 breast cancer patients from the Nottingham City Hospital. An independent second cohort of 737 patients from the Netherlands Cancer Institute to Antoni van Leeuwenhoek was used for evaluation. In the Nottingham Breast Cancer series, the TSR was an independent prognostic parameter for recurrence-free survival (RFS; HR 1.35, 95% CI 1.10–1.66, p = 0.004). The interaction term was statistically significant for grade and triple-negative status. Multivariate Cox regression analysis showed a more pronounced effect of the TSR for RFS in grade III tumors (HR 1.89, 95% CI 1.43–2.51, p < 0.001) and triple-negative tumors (HR 1.86, 95% CI 1.10–3.14, p = 0.020). Comparable hazard ratios and confidence intervals were observed for grade and triple-negative status in the ONCOPOOL study. The prognostic value of TSR was not modified by age, tumor size, histology, estrogen receptor status, progesterone receptor status, human epidermal growth factor receptor 2 status or lymph node status. In conclusion, patients with a stroma-high tumor had a worse prognosis compared to patients with a stroma-low tumor. The prognostic value of the TSR is most discriminative in grade III tumors and triple-negative tumors. The TSR was not modified by other clinically relevant parameters making it a potential factor to be included for improved risk stratification.     

Does the degree of cell lesion in breast cancer after inductive chemotherapy have any prognostic value?

During 1991 and 1992, 77 patients with breast cancer were treated with induction chemotherapy using the CMFV and FAC protocols at the Lublin Oncological Centre. The degree of cancer cell damage in the specimens obtained postoperatively was evaluated by microscopy. Complete or substantial damage of neoplastic cells was found in 29% of the cases; whereas minimal to no damage was found in 71% of specimens. After assessing the 5-year survival periods of our patients in relation to the degree of cancer cell damage after induction chemotherapy, a statistically significant correlation was noted. Five-year survival without cancer symptoms was observed in 64% of cases in which the cell damage was estimated as considerable, and only in 34% in which the damage was slight or not notable. A much weaker correlation was observed between the degree of breast cancer cell damage after inductive chemotherapy and clinical response.     

Do anthracyclines still have a role in adjuvant chemotherapy of breast cancer?

Anthracycline-based regimens became the standard of care for early breast cancer patients based on the survival advantage they provide over nonanthracycline-containing regimens. The addition of taxanes, and subsequently trastuzumab in HER2-overexpressing patients, to anthracyclines further improved their efficacy in several studies involving high-risk early breast cancer patients. Concern over toxicity initially surfaced after anthracyclines were reported to carry an increased risk of cardiotoxicity and secondary leukemia. Trastuzumab has since been shown to compound the risk of cardiotoxicity in patients who have received an anthracycline. This has led to the development of regimens featuring a taxane without an anthracycline; these protocols vary in design and have different toxicity and efficacy profiles. Ongoing investigations are centered on the optimization of nonanthracycline regimens, prospective exploration of molecular markers to identify populations of patients who will derive maximal benefit from anthracycline-based chemotherapy, and the identification of less cardiotoxic formulations of existing anthracycline agents. Perhaps most importantly, a rapidly growing understanding of the biological heterogeneity of breast cancer is likely to lead to an individualized standard of care guided by particular patient and tumor characteristics.     

The prognostic value of four interleukin-1 gene polymorphisms in caucasian women with breast cancer – a multicenter study

Background  

The proinflammatory cytokine interleukin-1 (IL-1) is known to play an important role in the carcinogenesis of breast cancer. Although IL-1 gene polymorphisms were reported to be associated with increased risk of breast cancer, their influence on survival of Caucasian breast cancer patients remains to be shown.     

Delivery of adjuvant sequential dose-dense FEC–Doc to patients with breast cancer is feasible,but dose reductions and toxicity are dependent on treatment sequence

Introduction This study prospectively investigates the impact of dose densification and altering sequence of fluorouracil, epirubicin and cyclophosphamide [FEC₁₀₀] and docetaxel [Doc] on dose delivery and tolerability of adjuvant chemotherapy in breast cancer patients. Methods 117 patients with high-risk primary operable breast cancer were randomized (1:1:2:2) to conventional (three cycles of 3-weekly FEC₁₀₀ then three cycles of 3-weekly Doc 100 mg/m² or reverse sequence) or dose-dense (dd) treatment (four 10- to 11-day cycles of FEC₇₅ then four 2-weekly cycles of Doc 75 mg/m², or the reverse). In the dd arms, pegfilgrastim was given on day 2 of each cycle, but only as secondary prophylaxis in conventional arms. Results The primary endpoint was the proportion of patients completing intended cycles at relative dose intensity ≥85% and this was achieved by 95% of patients in each group except for the ddDoc→FEC group (90%). Dose intensity in the dd arms increased by 48% for FEC and 11% for docetaxel, compared with the conventional arms (both P < 0.001). Doc dose reductions were more frequent with dd treatment and when Doc was given after FEC. Grade 3–4 neutropenia was significantly more frequent with conventional treatment, while fatigue and hand–foot syndrome were numerically more common with dd treatment, particularly when Doc was given after FEC. Discussion Delivery of adjuvant sequential ddFEC and Doc is feasible with growth factor support, and chemotherapy sequence appeared to affect delivery of target doses and toxicity.     

The methodology of quantitation of microvessel density and prognostic value of neovascularization associated with long‐term survival in Japanese patients with breast cancer

The present study updates results on methodology of quantitation of tumor neovascularization and those on the prognostic value of microvessel density (MVD) in breast cancer tissue previously published in the World J. Surg. 21: 49–56, 1997. The followup period of observation of the series was extended to 20 years, and new biological indicators (i.e., proliferating cell nuclear antigen (PCNA), cerbB2, and p53) were included in the analysis. There were 109 patients with primary breast cancer, from 1971 to 1979, followed up for a median of 14 years (range, 1–20). A representative median longitudinal section of each breast tumor was immunohistochemically stained with factor VIIIrelated antigen and analyzed. The three methods of identifying MVD were: (1) average microvessel count (AMC)/mm2, (2) central microvessel count (CMC)/mm2, and (3) highest microvessel count (HMC)/mm2. Thirtyone patients (28.4%) died of breast cancer. There was a relationship between MVD and peritumor blood vessel invasion (AMC: p = 0.0114, CMC: p = 0.0319, and HMC: p = 0.0009). However, there was no relationship between MVD and other factors. Univariate analysis showed that node status (p < 0.0001), histological grade (p < 0.0001), clinical tumor size (T) (p = 0.0002), PCNA (p = 0.0033), p53 (p = 0.0043), mitotic grade (p = 0.0092), AMC (p = 0.0214), and peritumor lymphatic vessel invasion (p = 0.0467) were significantly predictive of overall survival. HMC was borderline significant (p = 0.0702), while CMC and cerbB2 were not significant. Multivariate analysis showed that T (p = 0.0005), node status (p = 0.0053), and AMC (p = 0.0485) were independent factors, but neither CMC nor HMC was independent. AMC, a significant independent prognostic factor, might be a better method than the others for evaluating angiogenesis, but further and larger studies are warranted.     

Predictors of timing of adjuvant chemotherapy in older women with hormone receptor–negative,stages II–III breast cancer

Adherence to consensus guidelines for cancer care may vary widely across health care settings and contribute to differences in cancer outcomes. For some women with breast cancer, omission of adjuvant chemotherapy or delays in its initiation may contribute to differences in cancer recurrence and mortality. We studied adjuvant chemotherapy use among women with stage II or stage III, hormone receptor–negative breast cancer to understand health system and socio-demographic correlates of underuse and delayed adjuvant chemotherapy. We used Surveillance Epidemiology and End Results (SEER)-Medicare linked data to examine the patterns of care for 6,678 women aged 65 and older diagnosed with stage II or stage III hormone receptor–negative breast cancer in 1994–2002, with claims data through 2007. Age-stratified logistic regression was employed to examine the potential role of socio-demographic and structural/organizational health services characteristics in explaining differences in adjuvant chemotherapy initiation. Overall utilization of guideline-recommended adjuvant chemotherapy peaked at 43% in this population. Increasing age, higher co-morbidity burden, and low-income status were associated with lower odds of chemotherapy initiation within 4 months, whereas having positive lymph nodes, more advanced disease, and being married were associated with higher odds (P < 0.05). Health system–related structural/organizational characteristics and race/ethnicity offered little explanatory insight. Timely initiation of guideline-recommended adjuvant chemotherapy was low, with significant variation by age, income, and co-morbidity status. Based on these findings, future studies should seek to explore the more nuanced reasons why older women do not receive chemotherapy and why delays in care occur.     

Predictive value of neoadjuvant chemotherapy failure in breast cancer using FDG–PET after the first course

The aim of this study was to prospectively evaluate the predictive value of ¹⁸F-fluorodeoxyglucose–positron emission tomography (FDG–PET) to detect the absence of pathological response to preoperative chemotherapy in patients (pts) with breast cancer. 63 consecutive pts with non-metastatic, non-inflammatory breast cancer, eligible for neoadjuvant chemotherapy (3 FEC 100 followed by 3 Docetaxel) were enrolled. FDG–PET was performed just before the first as well as before the second course. Metabolic activity (tumour FDG uptake) was measured by standardised uptake value (SUV_max). Pts were classified as non-responders (NR) when the decrease of SUV_max in the primary tumour was less than 15% at the time of the second PET (EORTC 1999 criteria). The metabolic response in FDG–PET was correlated with WHO criteria (clinical evaluation and ultrasound and/or mammography) evaluated after three cycles, pathological complete response (pCR) after surgery (according to Sataloff classification) and 4-year relapse-free survival (RFS). The mean SUV_max decrease according to histological response was −52 ± 21% in case of pCR (Sataloff A) and 25 ± 34% in other cases (Sataloff B + C + D). Out of the 16 pts with no PET response (SUV decrease less than 15%), only one had a clinical response after the third cycle, and no pCR was observed. The 4-year RFS rate was significantly longer for metabolic responders than for NR (respectively, 85 vs. 44%; P = 0.01). This prospective study shows that a decrease in the SUV of less than 15% after the first chemotherapy course is a very potent predictor for failure of neoadjuvant chemotherapy, especially of pCR. It is interesting to note that this was shown despite the fact that the chemotherapy regimen was changed after the third course.     

A nested case–control study of adjuvant hormonal therapy persistence and compliance,and early breast cancer recurrence in women with stage I–III breast cancer

Background:

Non-persistence and non-compliance are common in women prescribed hormonal therapy for breast cancer, but little is known about their influence on recurrence.

Methods:

A nested case–control study of associations between hormonal therapy non-persistence and non-compliance and the risk of early recurrence in women with stage I–III breast cancer was undertaken. Cases, defined as women with a breast cancer recurrence within 4 years of hormonal therapy initiation, were matched to controls (1 : 5) by tumour stage and age. Conditional logistic regression was used to examine associations between early recurrence and hormonal therapy non-persistence and non-compliance.

Results:

Ninety-four women with breast cancer recurrence were matched to 458 controls. Women who were non-persistent (⩾180 days without hormonal therapy) had a significantly increased adjusted recurrence odds ratio (OR) of 2.88 (95%CI 1.11, 7.46) compared with persistent women. There was no significant association between low compliance (OR 1.30; 95% CI 0.74, 2.30) and breast cancer recurrence.

Conclusion:

Hormonal therapy non-persistence is associated with a significantly higher risk of early recurrence in women with stage I–III oestrogen receptor (ER)-positive breast cancer. This finding is consistent with results from randomized studies of hormonal therapy treatment duration and suggests that interventions to target modifiable risk factors for non-persistence are required.     

Is extracapsular tumour spread a prognostic factor in patients with early breast cancer?

Background

This study searched for extra capsular tumour spread (ECS) as a prognostic factor for recurrence in terms of Disease Free Survival (DFS) and Overall Survival (OS).

Patients and methods

For this study, from a retrospective database of the Doubs cancer registry, 823 eligible women with node positive breast cancer treated from February 1984 to November 2000 were identified. The following factors were evaluated: ECS, numbers of involved nodes, histological tumour grade, tumour size, status of estrogen and progesterone receptors, and age of patient. A Cox proportional hazards method was used to search for significant factors related to OS and DFS length.

Results

In the multivariate analysis, factors related to DFS length were found to be: tumour grade (aHR 0.76, 95 % CI 0.61–0.96, p = 0.02), ECS status (aHR 0.7, 95 % CI 0.49–0.96, p = 0.03), progesterone (PgR) status (aHR 0.63, 95 % CI 0.44–0.85 p = 0.008), number of nodes involved (aHR 0.75, 95 % CI 0.56–1, p = 0.05). The multivariate analysis for OS found as significant factors: tumour grade (aHR 0.76, 95 % CI 0.61–0.95; p = 0.02) and PgR status (aHR 0.8, 95 % CI 0.56–0.99, p = 0.02).

Conclusions

This study might suggest taking into account ECS status in the adjuvant decision-making process.     

Epirubicin dose and sequential hormonal therapy—Mature results of the HMFEC randomised phase III trial in premenopausal patients with node positive early breast cancer

BackgroundThe hormonal manipulation 5-Fluoro-uracil Epirubicin Cyclophosphamide (HMFEC) trial was developed at a time of uncertainty around the dose intensity of chemotherapy given to premenopausal patients with node positive breast cancer and to the benefits of tailored endocrine therapy in such patients.Patients and methodsHMFEC was a multi-centre, phase III, open label, randomised controlled trial with a 2 × 2 factorial design. Eligible patients were premenopausal with node positive early breast cancer; significant cardiac disease or uncontrolled hypertension was exclusion criterion. Patients were allocated to receive either eight cycles of FE₅₀C or FE₇₅C (given 3 weekly) with or without hormone manipulation (HM; tamoxifen or luteinising hormone releasing hormone (LHRH) agonists according to residual hormone levels at the end of chemotherapy) irrespective of ER status. The primary end-point was disease free survival (DFS). Principal analyses were by intention to treat (ITT); however, to reflect contemporary practice, subgroup analyses according to ER status were also conducted. The mature follow-up now available from this modest sized trial enables presentation of definitive results.ResultsBetween 1992 and 2000 a total of 785 patients were randomised into the HMFEC trial (203 FE₅₀C−HM, 191 FE₅₀C+HM, 198 FE₇₅C−HM, 193 FE₇₅C+HM). At a median follow-up of 7.4 years, 245 DFS events have been reported (92 ER−, 153 ER+/unknown). The effects on DFS were not statistically significantly different according to epirubicin dose (hazard ratio [HR] = 0.82, 95% confidence interval [CI] 0.63–1.06; p = 0.13 FE₇₅C versus FE₅₀C); however, FE₇₅C appeared to induce more alopecia and neutropenia. No statistically significant evidence was observed to support an improvement in DFS in patients allocated HM either overall (HR = 0.88, 95% CI 0.68–1.13; p = 0.32) or in patients with ER+/unknown disease (HR = 0.85, 95% CI 0.62–1.17; p = 0.32) although effect sizes are consistent with worthwhile clinical effects. Overall, there was no evidence of a difference in survival between any of the four treatment groups of the trial.ConclusionHigher doses of epirubicin cause more adverse events in the absence of clear improvement in overall survival. Endocrine therapy with either tamoxifen or goserelin provided no significant added benefit to cytotoxic chemotherapy in this group of patients.Trial Registration Number: ISRCTN98335268     

Dietary patterns and the risk of postmenopausal breast cancer in a German case–control study

Objective  

Dietary patterns have been inconsistently associated with breast cancer risk. We assessed dietary patterns in association with postmenopausal breast cancer risk using an exploratory approach.     

What is the value of hemoglobin as a prognostic and predictive factor in cancer?

Anemia is a frequently encountered complication in cancer, and is associated with fatigue and reduced quality of life. Retrospective analyses of data from patients with hematological malignancies and solid tumors provide evidence that a low baseline hemoglobin (Hb) level is a prognostic factor for poor outcome. Moreover, in some situations, low Hb is a negative predictive parameter in chemotherapy. The adverse impact of anemia has been documented in patients with lymphomas and leukemias, as well as in those with non–small-cell lung cancer, ovarian cancer, cervical cancer, renal cell carcinoma, head and neck cancer and other solid tumors. Studies in animal models support the role of low Hb levels as a negative prognostic and predictive factor. Although prospective clinical trials are still needed to confirm that Hb levels affect outcome, the available evidence suggests that there is more than one reason to pay attention to Hb levels in cancer patients: increasing Hb not only corrects anemia and thereby improves physical functioning and quality of life, but also may improve clinical outcomes.