Improvements in breast cancer survival over time,related to adjuvant treatment and node status

Background

There has been an increase in the use and effectiveness of adjuvant treatment for operable breast cancer and the aim of this study was to examine whether this has resulted in improved survival for all prognostic groups.

Methods

A retrospective study of 1517 patients with invasive breast cancer treated between 1980 and 2002 was carried out. The use of adjuvant treatment was compared between two time periods in patients based on nodal status, and survival was calculated by Kaplan–Meier life table analysis. Independent predictors for recurrence-free survival (RFS) were determined by Cox regression analysis.

Results

The use of adjuvant therapy increased for all prognostic groups. On multivariate analysis the use of radiotherapy and endocrine therapy was positively associated with RFS which was significant in the second time period. Outcome in node positive patients improved: five-year RFS from 59% to 76%, p < 0.01 and breast cancer specific survival (BCSS) from 70% to 83%, p < 0.01. However, there was no survival improvement in the larger group of node negative patients; BCSS 93% versus 95%, p = 0.99. Within the node negative group, patients with tumours ≥ 2 cm had an improved RFS from 80% to 88%, p = 0.02.

Conclusion

The increased use of adjuvant therapy was associated with an improved outcome in node positive patients. For node negative patients with good prognostic features the evidence of benefit was marginal.     

The impact of young age on breast cancer outcome

Aims

We conducted a retrospective analysis in order to evaluate the impact of age on women aged less than 35 years affected by breast cancer.

Materials and methods

Between January 1972 and December 2006, 346 patients aged less than 35 years underwent adjuvant treatment at Florence University. The mean age of the patient population was 32 years (range 22–35): 76 patients were under 30 years old, the remaining were above 30 years old.

Results

In our series, 215 patients received adjuvant radiotherapy to whole breast after conservative surgery, 131 patients underwent mastectomy without subsequent radiation therapy and 323 patients had lymphadenectomy; 191 patients received adjuvant chemotherapy, 73 with anthracycline-containing regimen. With a median time of 2.5 years (range 6 months to 27.6 years) local relapses were observed in 67 cases (19.4%). At the multivariate analysis of local disease-free survival, ductal and ductal plus lobular histotypes, having more than 3 positive nodes, and age emerged as independent significant relapse predictors (p = 0.018, p = 0.0005, p = 0.003 and p = 0.024, respectively). For the DSS analysis, the median follow-up was 6.8 years (range 0.6–36.7 years). At the multivariate analysis, age (p = 0.0038), positive nodes (p = 0.0035) and distant metastases (p < 0.0001) resulted to be independent death predictors. Patients younger than 30 had a worse prognosis. At the univariate analysis also local relapse resulted to be statistically significant (p = 0.0004).

Conclusions

Anthracycline-based chemotherapy seems to improve the outcome of these patients. However, there is an urgent need for tailored treatment investigations within the framework of randomized, controlled clinical trials.     

Normal tissue complication probability (NTCP) parameters for breast fibrosis: Pooled results from two randomised trials

Introduction

The dose–volume effect of radiation therapy on breast tissue is poorly understood. We estimate NTCP parameters for breast fibrosis after external beam radiotherapy.

Materials and methods

We pooled individual patient data of 5856 patients from 2 trials including whole breast irradiation followed with or without a boost. A two-compartment dose volume histogram model was used with boost volume as the first compartment and the remaining breast volume as second compartment. Results from START-pilot trial (n = 1410) were used to test the predicted models.

Results

26.8% patients in the Cambridge trial (5 years) and 20.7% patients in the EORTC trial (10 years) developed moderate-severe breast fibrosis. The best fit NTCP parameters were BEUD₃(50) = 136.4 Gy, γ50 = 0.9 and n = 0.011 for the Niemierko model and BEUD₃(50) = 132 Gy, m = 0.35 and n = 0.012 for the Lyman Kutcher Burman model. The observed rates of fibrosis in the START-pilot trial agreed well with the predicted rates.

Conclusions

This large multi-centre pooled study suggests that the effect of volume parameter is small and the maximum RT dose is the most important parameter to influence breast fibrosis. A small value of volume parameter ‘n’ does not fit with the hypothesis that breast tissue is a parallel organ. However, this may reflect limitations in our current scoring system of fibrosis.     

Adjuvant extension of chemotherapy after neoadjuvant therapy may not improve outcome in early-stage breast cancer

Introduction

Neoadjuvant chemotherapy (NAC) is equivalent to adjuvant therapy (AdC) in terms of survival and disease-free interval. Many institutions add AdC after NAC and surgery. However, such extended chemotherapy (ExC) is not evidence based. Study aim was to investigate if ExC improved disease-free (DFS) and overall survival (OS).

Patients and Methods

From 1998 to 2006 356 consecutive patients received NAC (45 pts), AdC (221 pts) or ExC (90 pts). We analysed these 3 groups to determine effects of ExC and to identify patients who might benefit. NAC consisted in 93% of 3–6 cycles of epirubicin + docetaxel, AdC comprised EC ± taxanes in 72%. Median age in the NAC, AdC, and ExC-groups was 54, 56 and 52 years with follow-up of 30, 57, and 55 months.

Results

After NAC, 35% achieved downstaging and 10% pathologic complete remission. Surprisingly ExC seemed to result in reduction of 5-year DFS: compared to 85% and 82% after NAC and AdC, DFS was 61% after ExC (p = 0.001). OS was not significantly affected (79, 91, and 78% after NAC, AdC and ExC, p = 0.13). In multivariate analysis after correction for age, menopausal status, stage, grading, hormone receptors, her2-status, radiotherapy and surgery, ExC seemed to adversely affect DFS (HR 2.15, p = 0.008), loco-regional and distant recurrence-rates (HR 3.0, p = 0.03 and HR 2.0, p = 0.02).

Discussion

In this single-center analysis ExC could not show advantages in terms of DFS and OS. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials. Until then, extended chemotherapy should be considered carefully. As in previous studies, no differences were found between NAC and AdC groups.     

Sentinel node biopsy in breast cancer has a greater node positivity rate than axillary node sample: Results from a retrospective analysis

Background

Sentinel node biopsy as a surgical method of axillary staging for early breast cancer has been widely accepted as an alternative to traditional four-node axillary node sampling, and is the recommended technique by the Association of Breast Surgery in the United Kingdom. In selected units axillary sampling has been compared with either radioisotope sentinel node or blue dye only techniques with comparable node positivity rates. There are no studies directly comparing combined method sentinel node biopsy (SNB) with conventional axillary (four) node sampling (ANS).

Methods

Data for all patients undergoing axillary staging by axillary node sample or sentinel node biopsy were collected, including those proceeding to axillary clearance as a second procedure, but excluding those undergoing axillary clearance as a first procedure.

Results

From January 2005 to January 2011, 641 axillary staging procedures were performed (SNB n = 231 (36.0%), ANS n = 410 (64.0%)). Baseline tumour characteristics were similar for the two groups except for a higher frequency of breast conservation in the SNB group (95.6 vs. 75.6%; p < 0.0001). The proportion of cases with positive nodes was higher in the SNB group (20.8 vs. 14.4%; p = 0.042). In patients who had presented with symptomatic disease, there was a significantly higher node positivity rate with SNB (30.9%) than with ANS (15.5%; p = 0.002), despite similar baseline characteristics in both groups.

Conclusion

Combined method sentinel node biopsy is more sensitive at detecting low volume axillary disease than traditional four-node sample.     

Sentinel lymph node biopsy is associated with improved survival compared to level I & II axillary lymph node dissection in node negative breast cancer patients

Objective

The few long-term follow-up data for sentinel lymph node (SLN) negative breast cancer patients demonstrate a 5-year disease-free survival of 96–98%. It remains to be elucidated whether the more accurate SLN staging defines a more selective node negative patient group and whether this is associated with better overall and disease-free survival compared with level I & II axillary lymph node dissection (ALND).

Methods

Three-hundred and fifty-five consecutive node negative patients with early stage breast cancer (pT1 and pT2 ≤ 3 cm, pN0/pN_SN0) were assessed from our prospective database. Patients underwent either ALND (n = 178) in 1990–1997 or SLN biopsy (n = 177) in 1998–2004. All SLN were examined by step sectioning, stained with H&E and immunohistochemistry. Lymph nodes from ALND specimens were examined by standard H&E only. Neither immunohistochemistry nor step sections were performed in the analysis of ALND specimen.

Results

The median follow-up was 49 months in the SLN and 133 months in the ALND group. Patients in the SLN group had a significantly better disease-free (p = 0.008) and overall survival (p = 0.034). After adjusting for other prognostic factors in Cox proportional hazard regression analysis, SLN procedure was an independent predictor for improved disease-free (HR: 0.28, 95% CI: 0.10–0.73, p = 0.009) and overall survival (HR: 0.34, 95% CI: 0.14–0.84, p = 0.019).

Conclusions

This is the first prospective analysis providing evidence that early stage breast cancer patients with a negative SLN have an improved disease-free and overall survival compared with node negative ALND patients. This is most likely due to a more accurate axillary staging in the SLN group.     

Hypofractionated whole breast irradiation for patients with large breasts: A randomized trial comparing prone and supine positions

Background and purpose

Comparison of acute toxicity of whole-breast irradiation (WBI) in prone and supine positions.

Materials and methods

This non-blinded, randomized, prospective, mono-centric trial was undertaken between December 29, 2010, and December 12, 2012. One hundred patients with large breasts were randomized between supine multi beam (MB) and prone tangential field (TF) intensity modulated radiotherapy (IMRT). Dose–volume parameters were assessed for the breast, heart, left anterior descending coronary artery (LAD), ipsilateral lung and contralateral breast. The primary endpoint was acute moist skin desquamation. Secondary endpoints were dermatitis, edema, pruritus and pain.

Results

Prone treatment resulted in: improved dose coverage (p < 0.001); better homogeneity (p < 0.001); less volumes of over-dosage (p = 0.001); reduced acute skin desquamation (p < 0.001); a 3-fold decrease of moist desquamation p = 0.04 (chi-square), p = 0.07 (Fisher’s exact test)); lower incidence of dermatitis (p < 0.001), edema (p = 0.005), pruritus (p = 0.06) and pain (p = 0.06); 2- to 4-fold reduction of grades 2–3 toxicity; lower ipsilateral lung (p < 0.001) and mean LAD (p = 0.007) dose; lower, though statistically non-significant heart and maximum LAD.

Conclusions

This study provides level I evidence for replacing the supine standard treatment by prone IMRT for whole-breast irradiation in patients with large breasts. A confirmatory trial in a multi-institutional setting is warranted.     

Phase II trial of proton beam accelerated partial breast irradiation in breast cancer

Background and purpose

Here, we report the results of our phase II, prospective study of proton beam accelerated partial breast irradiation (PB-APBI) in patients with breast cancer after breast conserving surgery (BCS).

Materials and methods

Thirty patients diagnosed with breast cancer were treated with PB-APBI using a single-field proton beam or two fields after BCS. The treatment dose was 30 cobalt gray equivalent (CGE) in six CGE fractions delivered once daily over five consecutive working days.

Results

All patients completed PB-APBI. The median follow-up time was 59 months (range: 43–70 months). Of the 30 patients, none had ipsilateral breast recurrence or regional or distant metastasis, and all were alive at the last follow-up. Physician-evaluated toxicities were mild to moderate, except in one patient who had severe wet desquamation at 2 months that was not observed beyond 6 months. Qualitative physician cosmetic assessments of good or excellent were noted in 83% and 80% of the patients at the end of PB-APBI and at 2 months, respectively, and decreased to 69% at 3 years. A good or excellent cosmetic outcome was noted in all patients treated with a two-field proton beam at any follow-up time point except for one. For all patients, the mean percentage breast retraction assessment (pBRA) value increased significantly during the follow-up period (p = 0.02); however, it did not increase in patients treated with two-field PB-APBI (p = 0.3).

Conclusions

PB-APBI consisting of 30 CGE in six CGE fractions once daily for five consecutive days can be delivered with excellent disease control and tolerable skin toxicity to properly selected patients with early-stage breast cancer. Multiple-field PB-APBI may achieve a high rate of good-to-excellent cosmetic outcomes. Additional clinical trials with larger patient groups are needed.     

IORT with electrons as boost strategy during breast conserving therapy in limited stage breast cancer: Long term results of an ISIORT pooled analysis

Purpose

Linac-based intraoperative radiotherapy with electrons (IOERT) was implemented to prevent local recurrences after breast conserving therapy (BCT) and was delivered as an intraoperative boost to the tumor bed prior to whole breast radiotherapy (WBI). A collaborative analysis has been performed by European ISIORT member institutions for long term evaluation of this strategy.

Material and methods

Until 10/2005, 1109 unselected patients of any risk group have been identified among seven centers using identical methods, sequencing and dosage for intra- and postoperative radiotherapy. A median IOERT dose of 10 Gy was applied (90% reference isodose), preceding WBI with 50–54 Gy (single doses 1.7–2 Gy).

Results

At a median follow up of 72.4 months (0.8–239), only 16 in-breast recurrences were observed, yielding a local tumor control rate of 99.2%. Relapses occurred 12.5–151 months after primary treatment. In multivariate analysis only grade 3 reached significance (p = 0.031) to be predictive for local recurrence development. Taking into account patient age, annual in-breast recurrence rates amounted 0.64%, 0.34%, 0.21% and 0.16% in patients <40 years; 40–49 years; 50–59 years and ?60 years, respectively.

Conclusion

In all risk subgroups, a 10 Gy IOERT boost prior to WBI provided outstanding local control rates, comparing favourably to all trials with similar length of follow up.     

Population-based validation of a policy change to use long-term androgen deprivation therapy for cT3–4 prostate cancer: Impact of the EORTC22863 and RTOG 85-31 and 92-02 trials

Purpose

After publication of EORTC-22863 trial, prolonged androgen deprivation therapy (ADT) combined with radiation therapy (RT) became standard policy for high-risk prostate cancer patients in British Columbia (BC) in 1997. We evaluated whether population-based survival improved after this policy change.

Patients and methods

Two cohorts comprising all patients with T3–T4 prostate cancer treated with curative-intent RT in BC were reviewed. The Early cohort (n = 730) was all patients treated between 1993 and 1995, and the Late cohort (n = 584) was all patients treated between 1999 and 2001. The BC Cancer Registry, which collects data on survival, was linked to RT and pharmacy databases. Duration of ADT, age, stage, grade, presenting PSA, and Charlson comorbidity index (CCI; none = 0, minor = 1, major = 2+), were abstracted from charts.

Results

Usage of ?6 months and ?18 months of neoadjuvant and adjuvant ADT increased from 14% and 1% to 97% and 59% (p < 0.0001). Baseline characteristics were similar, except for lower Gleason score (G2–6: 45% vs. 20%, G7: 35% vs. 48%, G8–10: 19% vs. 32%; p < 0.0001), higher T-stage (T4: 9% vs. 5%, p = 0.004) and higher comorbidity (CCI 0: 62% vs. 71%, CCI 1: 26% vs. 20%, CCI 2+: 11% vs. 9%, p = 0.002) in the Early cohort. Disease-specific survival adjusted for competing risks from other causes mortality was improved (90% vs. 86%, p = 0.042). On multivariate analysis, the Late cohort was independently associated with improved 8-year overall survival (76% vs. 64%, p = 0.0002).

Conclusions

This population-based study demonstrated improved overall survival following a policy change to use of prolonged ADT with curative RT for patients with T3–T4 prostate cancer.     

Effect of local therapy on locoregional recurrence in postmenopausal women with breast cancer in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial

Background and purpose

The TEAM trial investigated the efficacy and safety of adjuvant endocrine therapy consisting of either exemestane or the sequence of tamoxifen followed by exemestane in postmenopausal hormone-sensitive breast cancer. The present analyses explored the association between locoregional therapy and recurrence (LRR) in this population.

Material and methods

Between 2001 and 2006, 9779 patients were randomized. Local treatment was breast conserving surgery plus radiotherapy (BCS + RT), mastectomy without radiotherapy (MST-only), or mastectomy plus radiotherapy (MST + RT). Patients with unknown data on surgery, radiotherapy, tumor or nodal stage (n = 199), and patients treated by lumpectomy without radiotherapy (n = 349) were excluded.

Results

After a median follow-up of 5.2 years, 270 LRRs occurred (2.9%) among 9231 patients. The 5-years actuarial incidence of LRR was 4.2% (95% CI 3.3–4.9%) for MST-only, 3.4% (95% CI 2.4–4.2%) for MST + RT and 1.9% (95% CI 1.5–2.3%) for BCS + RT. After adjustment for prognostic factors, the hazard ratio (HR, reference BCS + RT) for LRR remained significantly higher for MST-only (HR 1.53; 95% CI 1.10–2.11), not for MST + RT (HR 0.78; 95% CI 0.50–1.22).

Conclusion

This explorative analysis showed a higher LRR risk after MST-only than after BCS + RT, even after adjustment for prognostic factors. As this effect was not seen for MST + RT versus BCS + RT, it might be explained by the beneficial effects of radiation treatment.     

Breast-conserving therapy with partial or whole breast irradiation: Ten-year results of the Budapest randomized trial

Background and purpose

To report the long-term results of a single-institution randomized study comparing the results of breast-conserving treatment with partial breast irradiation (PBI) or conventional whole breast irradiation (WBI).

Patients and methods

Between 1998 and 2004, 258 selected women with pT1 pN0-1mi M0, grade 1–2, non-lobular breast cancer without the presence of extensive intraductal component and resected with negative margins were randomized after BCS to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 × 5.2 Gy high-dose-rate (HDR) multi-catheter brachytherapy (BT; n = 88) or 50 Gy electron beam (EB) irradiation (n = 40). Primary endpoint was local recurrence (LR) as a first event. Secondary endpoints were overall survival (OS), cancer-specific survival (CSS), disease-free survival (DFS), and cosmetic results.

Results

After a median follow up of 10.2 years, the ten-year actuarial rate of LR was 5.9% and 5.1% in PBI and WBI arms, respectively (p = 0.77). There was no significant difference in the ten-year probability of OS (80% vs 82%), CSS (94% vs 92%), and DFS (85% vs 84%), either. The rate of excellent-good cosmetic result was 81% in the PBI, and 63% in the control group (p < 0.01).

Conclusions

Partial breast irradiation delivered by interstitial HDR BT or EB for a selected group of early-stage breast cancer patients produces similar ten-year results to those achieved with conventional WBI. Significantly better cosmetic outcome can be achieved with HDR BT implants compared with the outcome after WBI.     

Association of GSTP1 expression with resistance to docetaxel and paclitaxel in human breast cancers

Aims

It has been reported that glutathione S-transferase P1 (GSTP1) expression is implicated in resistance to taxanes (docetaxel and paclitaxel) in human breast cancer cells in vitro. In the study presented here, we examine whether GSTP1 expression is associated with resistance to docetaxel or paclitaxel in human breast cancers. We also investigated the relationship between GSTP1 methylation status and response to these taxanes.

Material and methods

Sixty two primary breast cancer patients were treated with docetaxel or paclitaxel as primary systemic treatment (PST). GSTP1 expression was detected immunohistochemically and the hypermethylation status GSTP1 gene was identified with a methylation specific primer assay.

Results

The mean tumor reduction rate for all patients (n = 62) was significantly (p < 0.001) higher in GSTP1 negative (0.73 ± 0.04; mean ± standard error) than GSTP1 positive (0.31 ± 0.09) tumors. The subset analysis showed that the mean reduction rate was significantly (p = 0.005) higher in GSTP1 negative (0.59 ± 0.06) than GSTP1 positive (0.11 ± 0.13) tumors in the docetaxel group as well as in the paclitaxel group (p = 0.006; GSTP1 negative tumors: 0.84 ± 0.05; GSTP1 positive tumors: 0.56 ± 0.08). On the other hand, GSTP1 methylation showed no significant association with the reduction rate.

Conclusion

Our present study has suggested that GSTP1 protein expression, but not GSTP1 methylation status, might be associated with response to docetaxel and paclitaxel. This suggests that GSTP1 immunohistochemical expression might be a potentially clinically useful predictive factor for response to docetaxel and paclitaxel.     

Preoperative chemoradiation in adenocarcinoma of the pancreas. A single centre experience advocating a new treatment strategy

Aims

To evaluate a single centre's experience with pancreatic carcinoma focused on preoperative chemoradiation therapy (CRT) for treatment of locally advanced pancreatic carcinoma. The aim of the present analysis was to evaluate the median overall survival time (OS) after preoperative CRT and to compare it with OS after primary resection of pancreatic carcinoma. In conclusion a new treatment strategy was developed using multimodality treatment for pancreatic carcinoma deemed to be resectable by CT-scan.

Patients and methods

Between 1995 and 2003, 302 patients with ductal adenocarcinoma of the pancreatic head and body were recorded prospectively and OS was analysed with regard to therapy.

Results

Fifty-eight patients were resected without any pretreatment and had an OS of 21 months. Twenty-one patients with initially unresectable tumours underwent CRT followed by resection and had an OS of 54 months, which was not significantly different from primary resection (p = 0.315). Lymph node metastasis was significantly reduced after CRT (p = 0.0029). OS for patients whose tumours could not be resected was 3–10 months, depending on tumour stage and consecutive therapy.

Conclusion

CRT pretreatment was effective in locally advanced pancreatic carcinoma and resulted in resection of tumours otherwise staged as non-resectable. This experience led to a randomized trial for patients who by CT are staged to have resectable cancer of the pancreatic head with the intent to increase curative resectability and survival by neoadjuvant CRT (ISRCTN78805636/NCT00335543).     

Comparison of 6 cycles versus 4 cycles of neoadjuvant epirubicin plus docetaxel chemotherapy in stages II and III breast cancer

Background

This phase III clinical study was designed to investigate whether 6 cycles of epirubicin plus docetaxel (ED) is more effective than 4 cycles of ED as neoadjuvant chemotherapy (NC) in patients with stage II or III breast cancer.

Patients and methods

Women with breast cancer that had tumors larger than 3 cm were prospectively randomized to receive 4 or 6 cycles of epirubicin 75 mg/m² and docetaxel 75 mg/m² every 3 weeks. The primary end point was the clinical response to NC.

Results

A total of 176 patients were randomly assigned, and 150 patients were assessable for efficacy and toxicity. Groups were well balanced for clinicopathologic parameters. The median age was 42 years (range 30–58). Overall clinical response was observed in 72% with ED4 and 82% with ED6. pCR was observed in 11% with ED4 and in 24% with ED6 (p = 0.047). 47% of the ED4 group underwent breast conserving surgery (BCS) whereas 58% of ED6 group underwent BCS. Grade 3/4 neutropenia was observed in 27% in ED4 and 31% in ED6. Febrile neutropenia occurred in 17% with ED4 and 19% with ED6. Grade 3 mucositis was observed in 8% with ED4 and in 6% with ED6.

Conclusion

Six cycles of ED enhanced the rates of pCR and BCS compared with 4 cycles without increasing treatment-related toxicities.     

Lymphatic mapping in patients with primary or recurrent breast cancer following previous axillary surgery

Aims

To evaluate the feasibility of lymphatic mapping in breast cancer patients after previous axillary surgery and to identify parameters associated with mapping failure.

Methods

Lymphatic mapping using peritumoural injection of blue dye and a radiocolloid was attempted in 30 patients with primary (n = 7) or recurrent (n = 23) breast cancer and a history of previous axillary lymph node dissection or sentinel node biopsy.

Results

Lymphatic mapping identified a mean number of 1.6 (range 1–3) lymph nodes in 19 of 30 patients (identification rate 63%). The lymph nodes were removed from the ipsilateral axilla (n = 13), the internal mammary chain (n = 2), both the internal mammary nodes and the axilla (n = 2), the interpectoral space (n = 1) and the contralateral axilla (n = 1). Four of 19 patients revealed a positive lymph node. Fifteen of 19 patients had a negative lymph node. Axillary lymph node dissection was done in 13 of 15 patients but found no positive nodes (false negative rate = 0). A negative lymphoscintigram (p < 0.001) and a number of more than 10 lymph nodes removed at the time of initial surgery (p = 0.02) were significantly associated with a mapping failure.

Conclusion

Lymphatic mapping following prior axillary surgery was accurate but associated with a low identification rate. The lymphatic drainage pattern was unpredictable and the use of a radionuclide was necessary for a successful mapping procedure.     

Patient reported outcome measures (PROMs) following forward planned field-in field IMRT: Results from the Cambridge Breast IMRT trial

Background

The use of intensity-modulated radiotherapy (IMRT) in breast cancer reduces clinician-assessed breast tissue toxicity including fibrosis, telangectasia and sub-optimal cosmesis. Patient reported outcome measures (PROMs) are also important as they provide the patient’s perspective. This longitudinal study reports on (a) the effect of forward planned field-in-field IMRT (∼simple IMRT) on PROMs compared to standard RT at 5 years after RT, (b) factors affecting PROMs at 5 years after RT and (c) the trend of PROMs over 5 years of follow up.

Methods

PROMs were assessed at baseline (pre-RT), 6, 24 and 60 months after completion of RT using global health (EORTC QLQ C30) and 4 breast symptom questions (BR23). Also, 4 breast RT-specific questions were included at 6, 24 and 60 months: change in skin appearance, firmness to touch, reduction in breast size and overall change in breast appearance since RT. The benefits of simple IMRT over standard RT at 5 years after RT were assessed using standard t-test for global health and logistic regression analysis for breast symptom questions and breast RT-specific questions. Clinical factors affecting PROMs at 5 years were investigated using a multivariate analysis. A repeated mixed model was applied to explore the trend over time for each of PROMs.

Results

(89%) 727/815, 84%, 81% and 61% patients completed questionnaires at baseline, 6, 24 and 60 months respectively. Patients reported worse toxicity for all four BR23 breast symptoms at 6 months, which then improved over time (p < 0.0001). They also reported improvement in skin appearance and breast hardness over time (p < 0.0001), with no significant change for breast shrinkage (p = 0.47) and overall breast appearance (p = 0.13). At 5 years, PROMs assessments did not demonstrate a benefit for simple IMRT over standard radiotherapy. Large breast volume, young age, baseline surgical cosmesis and post-operative infection were the most important variables to affect PROMs.

Conclusions

This study was unable to demonstrate the benefits of IMRT on PROMs at 5 years. PROMs are influenced by non-radiotherapy factors and surgical factors should be optimised to improve patients’ outcome. Only a small proportion of patients report moderate–severe breast changes post radiotherapy, with most PROMs improving over time. The difference in clinician assessment and PROMs outcome requires further investigation.     

Presence of mature DC-Lamp dendritic cells in sentinel and non-sentinel lymph nodes of breast cancer patients

Aim

Our study examined differences in the presence of mature, DC-Lamp⁺ DC in the SLN and non-SLN according to the extent of metastatic involvement.

Patients and methods

Paraffin blocks of the SLN and non-SLN from patients with primary breast cancer who had undergone SLN biopsy and axillary dissection were separated into three groups: (Group A) no tumor cell involvement in the SLN and non-SLN; (Group B) isolated tumor cells or micrometastases in the SLN, and tumor cell-free non-SLN; and (Group C) macrometastases in the SLN. One section of all the SLN and non-SLN was examined with immunohistochemistry using an anti-DC-Lamp-antibody. The densest area occupied by the DC-Lamp⁺ cells on each slide was quantified and recorded by an electronic imaging system. In this regard, the SLN and non-SLN were compared within the patients of each group using the Wilcoxon signed rank-test (p < 0.05).

Results

One hundred and fourteen SLN and 1258 non-SLN from 79 patients were examined. A significantly larger area was occupied by the DC-Lamp⁺ cells in the SLN compared to the non-SLN in Groups A (p = 0.024) and B (p = 0.009), whereas no significant difference was found within Group C (p = 0.107).

Conclusions

This study suggests that the DC-dependent immune response is altered during the process of metastasis formation and is primarily activated before and during formation of micrometastasis.     

Symptoms 10-17 years after breast cancer radiotherapy data from the randomised SWEBCG91-RT trial

Background

Postoperative radiotherapy decreases the risk for local recurrence and improves overall survival in women with breast cancer. We have limited information on radiotherapy-induced symptoms 10-17 years after therapy.

Material and methods

Between 1991 and 1997, women with lymph node-negative breast cancer were randomised in a Swedish multi-institutional trial to breast conserving surgery with or without postoperative radiotherapy. In 2007, 10-17 years after randomisation, the group included 422 recurrence-free women. We collected data with a study-specific questionnaire on eight pre-selected symptom groups.

Results

For six symptom groups (oedema in breast or arm, erysipelas, heart symptoms, lung symptoms, rib fractures, and decreased shoulder mobility) we found similar occurrence in both groups. Excess occurrence after radiotherapy was observed for pain in the breast or in the skin, reported to occur “occasionally” by 38.1% of survivors having undergone radiotherapy and surgery versus 24.0% of those with surgery alone (absolute difference 14.1%; p = 0.004) and at least once a week by 10.3% of the radiotherapy group versus 1.7% (absolute difference 8.6%; p = 0.001). Daily life and analgesic use did not differ between the groups.

Conclusions

Ten to 17 years after postoperative radiotherapy 1 in 12 women had weekly pain that could be attributed to radiotherapy. The symptoms did not significantly affect daily life and thus the reduced risk for local recurrence seems to outweigh the risk for long-term symptoms for most women.