Adjuvant radiation therapy after breast-conserving surgery in elderly women with early-stage breast cancer: controversy or consensus?

Breast-conservation therapy (BCT), which consists of breast-conserving surgery (BCS) and postoperative radiation therapy (RT), provides similar levels of local control and survival compared with mastectomy. Although the incidence of breast cancer increases with age and the proportion of elderly women in the population continues to increase, clinical trials of BCT have included few women aged > or = 65 years, limiting the ability to establish clear consensus regarding optimal therapy in this population. This article examines the literature on BCT in elderly women with early-stage breast cancer. A systematic search of the Medline and CancerLit databases was conducted to identify articles specifically addressing BCT in elderly women. The outcomes evaluated were local control, disease-free survival, overall survival, and treatment-related toxicities. The lack of consensus in breast-conservation management in elderly patients is highlighted by a paucity of prospective data and numerous retrospective series reporting diverse treatment approaches with conflicting results. The available evidence from BCT trials with and without age subgroup analyses support BCS with postoperative RT as the standard approach associated with the most favorable local control outcomes. A low-risk subset of patients in whom RT may be omitted without compromising local control remains to be defined. Despite these findings, the use of standard therapy significantly decreases with advancing patient age. Although data specifically addressing BCT in elderly patients are limited, age should not preclude consideration of standard treatment strategies to optimize local disease control. Modern clinical trials with representative samples of elderly patients evaluating cancer recurrence and survival as well as functional and quality-of-life outcomes are needed to define optimal breast-conservation management for this important patient population.     

Radiotherapy for stage I–II non-small cell lung cancer

Background. Surgery has been regarded as the standard treatment for patients with non-small cell lung cancer in the early stage, while radiotherapy has become an effective alternative for medically inoperable patients and those who refuse surgery. Methods. We reviewed the records of 31 patients with stage I–II non-small cell lung cancer treated by radiotherapy between 1980 and 1997. There were 15 patients in stage I and 16 in stage II. The variables analyzed for influence on cause-specific survival and loco-regional control were: age, performance status, clinical stage, tumor size, tumor site, radiation field, radiation dose, and combination with chemotherapy. Results. The overall and cause-specific 1-, 2-, 3-, and 5-years survival rates were 71% and 77%; 63% and 73%; 34% and 48%; and 17% and 32%, respectively. Five-year survival rate for patients with peripheral tumor in the lung was 72%, with 70% loco-regional control, while the 5-year survival rate of patients whose tumor originated in the central region was 20%, with 25% loco-regional control. These differences had marginal significance on univariate analysis (P = 0.07), but only tumor site (central vs peripheral ) showed marginal significant influence on cause-specific survival (P = 0.08) and loco-regional control (P = 0.07) on multivariate analysis. There were no fatal complications, including radiation-induced myelopathy. Conclusion. The present series showed satisfactory results with definitive radiotherapy for patients with medically inoperable stage I–II non-small cell lung cancer, with results similar to those in recent reports of radiotherapy. The only significant variable was that patients with peripheral tumors had a better prognosis than patients with central tumors. Received: March 26, 1999 / Accepted: August 9, 1999     

Access to multidisciplinary cancer care: is it linked to the use of breast-conserving surgery with radiation for early-stage breast carcinoma?

BACKGROUND: Breast-conserving surgery (BCS) with radiation (BCSR) requires a multidisciplinary care approach between surgeons and radiation oncologists. METHODS: This retrospective cohort study examined the use of preoperative radiation oncology consultation and whether use of or distance to this care was associated with treatment choice among 1188 women age > or = 65 years who were diagnosed with local or regional breast carcinoma in Washington State in 1994 and 1995. Study outcomes included rates of BCSR; BCS alone; and mastectomy; and radiation therapy among women who underwent BCS. RESULTS: Only 29% of patients in the current study consulted with a radiation oncologist preoperatively, and less than half of the patients (46.6%) consulted with either a medical oncologist or a radiation oncologist. Among women who underwent either BCSR or mastectomy, the odds of undergoing BCSR among women who had a preoperative radiation oncology consultation were 6.7 times the odds of women who did not have the consultation (P < or = 0.001). Similarly, the odds of receiving radiation therapy among women who underwent BCS and had a preoperative radiation oncology consultation were 5 times the odds of women who did not have the consultation (P < 0.001). The 3.4% of women who lived > 50 miles from the radiation therapy center had the lowest BCSR rate (15.8%) and had the lowest radiation therapy rate among women who underwent BCS (54.5%), although these findings were not statistically significant in adjusted analyses. CONCLUSIONS: A preoperative visit with a radiation oncologist was associated strongly with BCSR use. More should be done to evaluate the role of multidisciplinary consultation in the decision to use BCSR.     

Is elective nodal irradiation beneficial in patients with pathologically negative lymph nodes after neoadjuvant chemotherapy and breast-conserving surgery for clinical stage II–III breast cancer? A multicentre retrospective study (KROG 12-05)

Background:

To evaluate the effects of elective nodal irradiation (ENI) in clinical stage II–III breast cancer patients with pathologically negative lymph nodes (LNs) (ypN0) after neoadjuvant chemotherapy (NAC) followed by breast-conserving surgery (BCS) and radiotherapy (RT).

Methods:

We retrospectively analysed 260 patients with ypN0 who received NAC followed by BCS and RT. Elective nodal irradiation was delivered to 136 (52.3%) patients. The effects of ENI on survival outcomes were evaluated.

Results:

After a median follow-up period of 66.2 months (range, 15.6–127.4 months), 26 patients (10.0%) developed disease recurrence. The 5-year locoregional recurrence-free survival and disease-free survival (DFS) for all patients were 95.5% and 90.5%, respectively. Pathologic T classification (0−is vs 1 vs 2–4) and the number of LNs sampled (<13 vs ⩾13) were associated with DFS (P=0.0086 and 0.0012, respectively). There was no significant difference in survival outcomes according to ENI. Elective nodal irradiation also did not affect survival outcomes in any of the subgroups according to pathologic T classification or the number of LNs sampled.

Conclusions:

ENI may be omitted in patients with ypN0 breast cancer after NAC and BCS. But until the results of the randomised trials are available, patients should be put on these trials.     

Metastatic relapse of stage I–III breast cancer in New Zealand

Purpose

This study aims to investigate the factors that influence the risk of metastatic relapse in women presenting with stage I-III breast cancer in New Zealand.

Methods

The study included women diagnosed with stage I–III breast cancer. Cumulative incidence of distant metastatic relapse was examined with the Kaplan–Meier method by cancer stage and subtype. Cox proportional hazards models were used to estimate the adjusted hazard ratio of developing recurrent metastatic breast cancer by cancer stage and biomarker subtype after adjustment for other factors.

Results

A total of 17,543 eligible women were identified. The 5-year cumulative incidence of metastatic recurrence was 3.7% for stage I, 13.3% for stage II and 30.9% for stage III disease. The adjusted hazard ratios (HR) of stage II and stage III breast cancer developing metastatic disease were 2.07 and 4.82 compared to stage I. The adjusted risk of distant metastatic relapse was highest for luminal B HER2- cancers (adjusted HR: 1.59 compared to luminal A disease). Higher grade cancers were associated with a higher risk of metastases. After adjustment, women aged 60–69 years and Asian women had the lowest risk of distant metastatic relapse.

Conclusions

The prognosis of women with locally invasive breast cancer differs greatly with the chance of developing metastatic disease depending on the stage of disease at diagnosis and the subtype. Grade of disease at diagnosis was also important. Māori or Pacific ethnicity did not influence the risk of developing metastatic disease, although Asian women seemed less likely to develop metastases.

     

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.     

Detection of extra-axillary lymph node involvement with FDG PET/CT in patients with stage II–III breast cancer

PurposeThe aim of this prospective study was to assess the incidence of extra-axillary lymph node involvement on baseline FDG PET/CT in patients with stage II–III breast cancer scheduled for neo-adjuvant chemotherapy.MethodsPatients with invasive breast cancer of >3 cm and/or proven axillary lymph node metastasis were included for before neo-adjuvant chemotherapy. Baseline ultrasound of the infra- and supraclavicular regions was performed with fine-needle biopsy as needed. Subsequently FDG PET/CT was performed. All visually FDG-positive nodes were regarded as metastatic based on the previously reported high specificity of the technique.ResultsSixty patients were included. In 17 patients (28%) extra-axillary lymph nodes were detected by FDG PET/CT, localised in an intra-mammary node (1 lymph node in 1 patient), mediastinal (2 lymph nodes in 2 patients), internal mammary chain (9 lymph nodes in 8 patients), intra- and interpectoral (6 lymph nodes in 4 patients), infraclavicular (5 lymph nodes in 4 patients) and in the contralateral axilla (3 lymph nodes in 2 patients). Ultrasound-guided cytology had detected extra-axillary lymph node involvement in seven of these patients, but was unable to detect extra-axillary nodes in the other 10 patients with positive extra-axillary lymph nodes on FDG PET/CT. Radiotherapy treatment was altered in 7 patients with extra-axillary involvement (12% of the total group).ConclusionsFDG PET/CT detected extra-axillary lymph node involvement in almost one-third of the patients with stage II–III breast cancer, including regions not evaluable with ultrasound. FDG PET/CT may be useful as an additional imaging tool to assess extra-axillary lymph node metastasis, with an impact on the adjuvant radiotherapy management.     

Complications after breast cancer surgery in patients treated with concomitant preoperative chemoradiation: a case–control analysis

Background Nearly 60% of breast cancer cases in Mexico are in advanced stages. At our institution, concomitant preoperative chemoradiation is being used in patients with advanced breast cancer. In the present study, we evaluated the postoperative wound complications and risk factors associated. Patients and methods The study included breast cancer patients from January 2000 to December 2002 treated with concomitant preoperative chemoradiation and mastectomy. Wound complication rates were described along with a nested case–control analysis to evaluate risk factors for postoperative major wound complications. Results We evaluated 360 patients treated with preoperative chemoradiation. About 165 patients (45.8%) developed a wound complication (infection and/or flap necrosis); 60 (16.6%) patients had a surgical site infection (SSI) and 61 (16.9%), flap necrosis; 44 (12.2%) developed both complications, and 25 (6.9%) experienced late dehiscence after suture removal. Epidermolysis, seroma, and hematoma ocurred in 93 (25.8%), 80 (22.2%), and 12 patients (3.3%), respectively. Case–control analysis was conducted in 335 patients. After logistic regression analysis, the sole variable found associated with SSI and/or flap necrosis was epidermolysis (OR = 8.81, 95% CI = 4.52–17.18). Although not significant and of lesser magnitude, adjusted risk estimates of overweight, age >50 years, and type of mastectomy showed the same trend. Conclusions Postoperative wound complications were not different from those observed in non-radiated patients, but its rate was higher. Epidermolysis was associated with SSI and/or flap necrosis. Careful surgical technique should be encouraged.     

Phase I–II trial of prolonged gemcitabine infusion plus paclitaxel as a biweekly schedule for advanced breast cancer patients pretreated with anthracyclines

Purpose

Paclitaxel (PACL) plus gemcitabine (GEM) is an effective regimen for advanced breast cancer patients pretreated with anthracyclines. A prolonged GEM infusion at a fixed dose rate (FDR) of 10 mg/m²/min produces higher levels of intracellular active metabolites of GEM when compared with a standard 30-min infusion. In the present phase I/II trial, we investigated the association of FDR GEM plus PACL.

Methods

1,200 mg/m² was the dose of GEM recommended for the phase II study, in which patients received PACL at 150 mg/m², followed by FDR GEM at 1,200 mg/m² (total GEM infusion time = 120 min), both drugs administered biweekly.

Results

Forty-two anthracycline-pretreated advanced breast cancer patients with disease recurrence following at least one line of chemotherapy were enrolled. Two (4.8%) and 12 (33.3%) patients experienced a complete and partial response, respectively, for an overall response rate of 38.1% (95% CI 23.4–52.8%). Median progression free survival and overall survival were 5 and 19.9 months, respectively. No statistically significant association was noted between in situ protein expression of RRM1 and BRCA1 (as assessed by immunofluorescence combined with automated quantitative analysis) and response to treatment in 15 patients with tissue available for analysis. Toxicity was mostly mild to moderate, mainly consisting of G3–G4 neutropenia (9.6%) and hypertransaminasemia (9.5%).

Conclusions

Biweekly FDR GEM in combination with PACL is an active and safe regimen for advanced breast cancer patients pretreated with anthracyclines. A prolonged infusion regimen of GEM does not seem to improve the efficacy of a standard 30-min infusion.     

Does margin width impact breast cancer recurrence rates in women with breast conserving surgery for ductal carcinoma in situ?

Purpose

Controversy remains regarding the optimal margin width for patients with ductal carcinoma in situ (DCIS) who undergo breast conserving surgery (BCS).

Methods

Women with a primary DCIS diagnosis were enrolled in a statewide population-based cohort from 1997 to 2006. Patients were surveyed every two years with follow-up data available through 2016. Surgical pathology reports were collected for 559 participants following breast conserving surgery. Multivariable Cox proportional hazard models evaluated relationships between locoregional recurrence (LRR) and margin width in the presence or absence of adjuvant radiation therapy while controlling for age, menopausal status and duration of endocrine therapy use.

Results

The majority of women in this study were over 50yo (74%), 34% had high grade disease, and 77% underwent radiation. The overall LRR rate was 12%. A LRR occurred in 46 women who had radiation (11%) and 23 women who did not undergo radiation (19%). Univariate analysis identified smaller margin width, younger age, premenopausal status, no radiotherapy, and shorter endocrine therapy use associated with LRR. Multivariable models demonstrated that close margins (<?2 mm) were associated with an increased risk of recurrence when compared to margins?≥?2 mm in width whether women received radiation (HR 1.98 CI 0.87–4.54) or not (HR 1.32 CI 0.27–6.49), but confidence intervals were wide.

Conclusions

In this study, patients with DCIS and close margins were less likely to experience recurrence after routine re-excision to margins greater than 2 mm.

     

Omitting radiotherapy in women ≥ 65 years with low-risk early breast cancer after breast-conserving surgery and adjuvant endocrine therapy is safe

Purpose

The aim of this study was to verify if radiotherapy (RT) safely can be omitted in older women treated for estrogen-receptor positive early breast cancer with breast-conserving surgery (BCS) and endocrine therapy (ET).

Incidence of second primary malignancy after breast cancer and related risk factors—Is breast-conserving surgery safe? A nested case–control study

Risk of second primary malignancy (SPM) is increasing. We aimed to assess the incidence and related risk factors of SPM among breast cancer (BC) patients from this nested case–control study using the SEER database. BC patients with SPM were identified as the case group and SPM-free patients were defined as the control group. Propensity score matching of cases with controls by the year of the first primary BC diagnosis was conducted at the ratio of 1:5, and 97,242 BC patients were enrolled from 1998 to 2013 after the matching. The incidence of SPM in BC patients stratified by age groups and cancer sites was compared to the general population using the adjusted standardized incidence ratio (SIR) and the risk factors for SPM were examined using Cox proportional hazard regressions. Our study showed BC patients had excess risk for SPM than the general population (adjusted SIR for all cancer sites = 12.94, p < 0.001) and the incidence of SPM among them decreased with age. The risk of SPM was significantly related to the following demographical and clinical variables: age (40–59 vs. 18–39, HR = 1.33; 60–79 vs. 18–39, HR = 2.39; ≥80 vs. 18–39, HR = 2.84), race (black vs. white, HR = 1.12), histological type (lobular BC vs. ductal BC, HR = 1.15), radiotherapy (HR = 1.33), marital status (married vs. single, HR = 0.88) and estrogen receptor status (positive vs. negative, HR = 0.85). Consistent results were found in subgroup analysis stratified by contralateral-breast SPMs and nonbreast SPMs.     

Foot posture in female patients 5 years after breast-conserving surgery: a case–control study

Purpose

Along with the improvement in the outcomes of breast cancer treatment being observed in the recent years, long-term studies to assess distant adverse effects of the treatment have become increasingly important. The objective of this study was to assess the foot posture in patients subjected to breast-conserving therapy. The assessment was made 5 years after the surgical procedure.

Methods

116 female patients (mean age of 58.75 years) were qualified into a case–control study. Foot posture on the operated breast side (F1) as well as on the contralateral side (F2) was evaluated using a computer-based foot analysis tool as an extension of projection moiré-based podoscopic examination. Comparisons were made for the following parameters: limb load, L—foot length, W—foot width, L/W—Wejsflog index, ALPHA—hallux valgus angle, BETA—little toe varus angle, GAMMA—heel angle, KY—Sztriter–Godunov index, CL—Clarke’s angle, HW—heel width.

Results

Five years after BCT, patients placed higher load on the foot on the side of the healthy breast (p = 0.0011). No statistically significant differences were observed between F1 and F2 with respect to other foot posture parameters (p > 0.05). No statistically significant differences were observed in foot posture parameters in patients having undergone BCT + ALND (axillary lymph node dissection) procedure as compared to patients subjected to BCT + SLNB (sentinel lymph node biopsy) procedure (p > 0.05).

Conclusions

No changes in foot posture were observed in patients 5 years after the BCT procedure. The type of the surgical procedure related to the lymph nodes within the axillary fossa has no effect on changes in foot posture.

     

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.     

Do we need to routinely perform cavity shaving with breast-conserving surgery for breast cancer? A systematic review and meta-analysis

AimsTo evaluate comparative outcomes of breast-conserving surgery (BCS) of breast cancer with and without cavity shaving.MethodsA systematic search of multiple electronic data sources was conducted, and all randomised controlled trials (RCTs) comparing BCS with or without cavity shaving for breast cancer were included. Positive margin rate, second operation rate, operative time, post-operative haematoma, cosmetic appearance and budget cost were the evaluated outcome parameters for the meta-analysis.ResultsSix RCTs reporting a total number of 971 patients; 495 of these underwent BCS plus shaving (BCS + S), and 473 underwent BCS alone were included. BCS + S showed significantly lower positive margin rate (Risk Ratio [RR] 0.40, P = 0.00001) and second operation rate (RR 0.38, P = 0.00001). BCS + S demonstrated longer operative time than BCS (79 ± 4 min vs 67 ± 3 min, Mean Difference 12.14, P = 0.002), and there was no significant difference in the risk of post-operative haematoma (RR 0.33, P = 0.20).ConclusionBCS + S is superior to BCS in terms of positive margins rate and second operation rate. Operative time is longer when cavity shaving is performed.     

Pre-chemotherapy 18F-FDG PET/CT upstages nodal stage in stage II–III breast cancer patients treated with neoadjuvant chemotherapy

In breast cancer patients treated with neoadjuvant chemotherapy (NAC) the number of tumor-positive nodes can no longer reliably be determined. Furthermore, ultrasound (US) seems suboptimal for the detection of N3-disease. Therefore we assessed the proportion of breast cancer patients treated with NAC in which pre-chemotherapy 18F-FDG PET/CT detected ≥4 axillary nodes or occult N3-disease, upstaging nodal status and changing risk estimation for locoregional recurrence (LRR). Conventional regional staging consisted of US with fine needle aspiration and/or sentinel lymph node biopsy. Patients were classified as low-risk (cT2N0), intermediate-risk (cT0N1, cT1N1, cT2N1, cT3N0), or high-risk (cT3N1, cT4, cN2–3) for LRR. The presence and number of FDG-avid nodes were evaluated and the proportion of patients that would be upstaged by PET/CT, based on detection of ≥4 FDG-avid axillary nodes defined as cN2(4+) or occult N3-disease, was calculated. In total, 87 of 278 patients were considered high-risk based on conventional staging. PET/CT detected occult N3-disease in 5 (11 %) of 47 low-risk patients. In 144 intermediate-risk patients, PET/CT detected ≥4 FDG-avid nodes in 24 (17 %) patients and occult N3-disease in 22 (15 %) patients, thereby finally upstaging 38 (26 %) of intermediate-risk patients. Of 43 (23 %) upstaged patients, 18 were ypN0, 12 were ypN1, and 13 were ypN2–3. Pre-chemotherapy PET/CT is valuable for selection of breast cancer patients at high risk for LRR. In our population, 23 % of patients treated with NAC were upstaged to the high-risk group based on PET/CT information, potentially benefiting from regional radiotherapy.     

Successful perioperative management for a breast cancer patient with Bernard–Soulier syndrome

We herein report the first case of a Bernard–Soulier syndrome (BSS) patient undergoing a surgical procedure for breast cancer. BSS is a rare hereditary thrombocytopathy associated with defects of the platelet glycoprotein complex glycoprotein Ib/V/IX and characterized by large platelets, thrombocytopenia, and severe bleeding symptoms. Because of the rarity of BSS, there are as yet no defined protocols for the perioperative management, which can be very complex and challenging in patients with coagulopathies, in particular BSS. In this case we successfully performed both an interventional examination as well as mastectomy with axillary lymph node dissection, under the preventive and intermittent transfusion of platelets. No intra- or postoperative bleeding complications occurred. Unfortunately, the patient was diagnosed as having metastatic disease involving liver, lungs, and bones 10 months after the surgery. She had received 1st, 2nd, and 3rd line chemotherapy without severe adverse events. However, gastrointestinal bleeding appeared after she was treated with 4th line chemotherapy. Finally, she succumbed 22 months after the breast surgery.