Radiation-induced dermatitis is a common side effect of breast irradiation, with hypofractionation being a well-known risk factor. In the context of the widespread adoption of hypofractionated breast radiotherapy, we evaluated the effect of hypofractionated radiotherapy on the incidence of skin toxicity in patients receiving adjuvant chemotherapy.
Patients and Methods
We retrospectively reviewed the records of patients with breast cancer treated from 2004 to 2006 at a single institution. Patients undergoing lumpectomy with or without adjuvant chemotherapy followed by hypofractionated radiotherapy consisting of 42.4 Gy in 16 fractions were included in the study. Using cosmetic and skin toxicity scales, all patients were evaluated weekly during treatment and at scheduled follow-up visits with the radiation oncologist.
During the study period, 162 patients underwent radiotherapy, and 30% of those (n = 48) received chemotherapy. Radiotherapy boost to the tumour bed was more common in the chemotherapy group [n = 20 (42%)] than in the radiotherapy-alone group [n = 30 (26%)]. We observed no statistically significant difference between the groups with regard to acute skin toxicity of grade 3 or higher (2.1% in the chemotherapy group vs. 4.4% in the radiation-alone group, p = 0.67) or of grades 1–2 toxicity (62.5% vs. 51.7% respectively, p = 0.23). There was also no significant difference in late grade 3 or higher skin toxicity between the groups (2.1% vs. 0% respectively, p = 0.30) or in grades 1–2 toxicity (20.8% vs. 25.5% respectively, p = 0.69). Similarly, excellent or good cosmetic result scores were similar in both groups (p = 0.80)
In our single-institution review, we observed no adverse effects of chemotherapy in combination with hypofractionated whole-breast irradiation. Further investigations are necessary to better elucidate the effects of chemotherapy on skin toxicity in the context of hypofractionated irradiation.
Breast cancer; hypofractionated radiotherapy; chemotherapy; skin toxicity
Psoriasis is a multi-factorial disease with various clinical manifestations. We present a case of unilateral psoriasis associated with ipsilateral lymphedema that developed after mastectomy for breast cancer. A 42-year-old Korean woman was referred to our clinic with a 1-month history of multiple erythematous scaly patches on the right arm, back, and breast and was diagnosed with psoriasis by a skin biopsy. Three years previously, she had been diagnosed with breast cancer (T1N2), underwent a right quadrantectomy and axillary lymph node dissection, and completed adjuvant chemotherapy followed by high-dose adjuvant radiotherapy. She had started rehabilitation therapy on the right arm for secondary lymphedema 30 months previously. Because of the long interval between radiation and psoriasis, we speculated that changes in the local milieu caused by the lymphedema might be a causative factor. We hereby report a rare case of unilateral psoriasis following post-mastectomy lymphedema.
Breast cancer; Lymphedema; Psoriasis; Unilateral
The surgical treatment of early breast cancer has evolved from the removal of the entire breast and surrounding tissues (mastectomy) to the removal of the tumour together with a margin of healthy tissue (lumpectomy). Adjuvant radiotherapy, however, is still mainly given to the whole breast. Furthermore, external beam radiotherapy is often given several months after initial surgery and requires the patient to attend the radiotherapy centre daily for several weeks. A single fraction of radiotherapy given during surgery directly to the tumour bed (intraoperative radiotherapy) avoids these problems. The rationale and level-1 evidence for the safety and efficacy of the technique are reviewed.
Background and purpose: Radiotherapy in breast cancer patients is limited by lung tissue tolerance. Two complications involving the lung are known: radiation pneumonitis (RP) and radiation fibrosis. The aim of the study was to evaluate the pattern of bronchoalveolar lavage (BAL) in patients with RP after radiotherapy for breast cancer in symptomatic and asymptomatic patients.
Material and methods: Sixty-five female patients (mean age 58.3 yrs) with RP after radiotherapy for breast cancer were included in the study. The majority of patients had previous breast surgery (mastectomy or lumpectomy and axillary dissection) and received doses of radiations of 45-50Gy. All patients had adjuvant chemotherapy with cyclophosphamide, 5-fluorouracil, and epirubicin or methotrexate.
Results: All patients had an infiltrate or consolidation on chest radiography confined to the upper lobe of the irradiated lung, as marker of RP. Based on the presence or absence of symptoms, we divided the patients in 2 groups: 49 patients (75.4%) with symptomatic RP (fever, cough, dyspnea, chest pain and fatigue) and 16 patients (24.6%) without any symptom. Symptomatic RP patients had a BAL with significant increase in total cells (18.0±12.2 x106 cells•100mL-1) when compared to BAL in asymptomatic patients (11.9±6.2 x106 cells•100mL-1), p=0.01. Lymphocytosis in BAL was significantly increased in symptomatic group, compared with asymptomatic one (35.4±18.7% vs. 26.1±14.3%, p=0.045), with predominance of T lymphocytes (CD3). It was also a predominance of CD4 lymphocytes in all patients, but the CD4/CD8 ratio was inside normal range in the majority of cases. Five patients had clinical features of bronchiolitis obliterans organizing pneumonia (BOOP) secondary to irradiation with increased percentages of lymphocytes, neutrophils, eosinophils, and mast cells in BAL and one patient without history of atopic disease had a percentage of 40% eosinophils. Only a mild reduction in diffusing capacity for carbon monoxide was seen in both groups on pulmonary function tests. The lung volumes were normal in all patients.
Conclusions: Lymphocytic alveolitis was the marker of radiation pneumonitis in all patients. The degree of the inflammatory reaction of the lungs was correlated with the presence of symptoms. The lymphocytic alveolitis consisted mainly of T lymphocytes, with a predominance of CD4 subset in both groups, but the CD4/CD8 ratio remained mostly into normal range.
radiation pneumonitis; breast cancer; bronchoalveolar lavage; lymphocytosis
Standard 3D-CRT after BCS may cause skin toxicity with a wide range of intensity including acute effects like erythema or late effects. In order to reduce these side effects it is mandatory to identify potential factors of influence in breast cancer patients undergoing standard three-dimensional conformal radiation therapy (3D-CRT) of the breast and modern systemic therapy.
Between 2006 and 2010 a total of 211 breast cancer patients (median age 52,4 years, range 24–77) after BCS consecutively treated in our institution with 3D-CRT (50 Gy whole breast photon radiotherapy followed by 16 Gy electron boost to the tumorbed) were evaluated with special focus on documented skin toxicity at the end of the 50 Gy-course. Standardized photodocumentation of the treated breast was done in each patient lying on the linac table with arms elevated. Skin toxicity was documented according to the common toxicity criteria (CTC)-score. Potential influencing factors were classified in three groups: patient-specific (smoking, age, breast size, body mass index = BMI, allergies), tumor-specific (tumorsize) and treatment-specific factors (antihormonal therapy with tamoxifen or aromatase inhibitors, chemotherapy). Uni- and multivariate statistical analyses were done using IBM SPSS version 19.
After 50 Gy 3D-CRT to the whole breast 28.9% of all 211 patients had no erythema, 62.2% showed erythema grade 1 (G1) and 8.5% erythema grade 2. None of the patients had grade 3/4 (G3/4) erythema.
In univariate analyses a significant influence or trend on the development of acute skin toxicities (erythema G0 versus G1 versus G2) was observed for larger breast volumes (p=0,004), smoking during radiation therapy (p=0,064) and absence of allergies (p=0,014) as well as larger tumorsize (p=0,009) and antihormonal therapy (p=0.005).
Neither patient age, BMI nor choice of chemotherapy showed any significant effect on higher grade toxicity. In the multivariate analysis, factors associated with higher grade skin toxicity were larger breast target volume (p=0,003), smoking (p=0,034) and absence of allergies (p=0,002).
Patients treated in this study showed less objectively documented skin toxicity after 50 Gy 3D-CRT compared to similar patient cohorts. Factors associated with higher grade skin toxicity were smoking during 3D-CRT, absence of allergies and larger breast volumes.
Skin toxicity; Breast cancer; External beam radiotherapy
Oncologists once downplayed the adjuvant role of radiotherapy after mastectomy. A decade ago, lacking a survival benefit, studies demonstrating late fatal myocardial infarctions nearly put a stop to any referrals of postoperative high-risk women to radiation oncology. The potential survival benefits of adjuvant radiotherapy may be overshadowed by inadequate technique leading to late cardiac deaths. Is it possible to cover the chest wall, internal mammary lymph chain, supraclavicular, and, where indicated, the axillary nodes and keep the dose to the coronary arteries and the lung to well within tolerance? A modern five-field comprehensive technique can deliver less cardiac and lung irradiation than the standard three-field technique, i.e. supraclavicular field matched to broad tangential fields. Linear accelerators with 4 megavolt (MV) to 6 MV photons, a full spectrum (6 MV to 20 MV) of electron energies, and meticulous computerized treatment planning based on multiple computed tomography planes allow an experienced physics/dosimetry team to treat all target sites while wrapping the dose around critical normal tissues.
Whether to offer postmastectomy radiation to women with one to three positive nodes after adjuvant chemotherapy treatment has been the subject of intense discussion since the publication of two major randomized prospective trials. Although before these studies radiotherapy after mastectomy was an established treatment for women with four or more positive axillary nodes, existing data did not justify its use in patients with less extensive nodal involvement. Now, with results from these studies showing improved survival after radiotherapy in all node-positive premenopausal and perimenopausal women, with perhaps its greatest benefit in women with 1–3 positive nodes, practice patterns are again shifting toward strong consideration of treatment in women with less tumor nodal involvement.
Radiotherapy has an established role in reducing the local relapses in breast cancer patients. The objective of this review was to investigate whether radiotherapy or its omission after breast surgery has measurable consequences on local tumor recurrence and patient survival. The late excess of cardiac deaths has also been published in various reports but important advances in the delivery of radiotherapy have overcome this problem to the extent that, excess cardiac deaths do not appear to be occurring in more recent trials. In this article some recent data, suggesting that radiotherapy following mastectomy and/or breast conserving surgery has a beneficial effect on survival is reviewed. Omission of radiotherapy is associated with a large increase in risk of ipsilateral breast tumor recurrence and with a small increase in the risk of patient’s mortality.
Radiotherapy; Breast cancer; recurrence; Mortality
Two hundred patients with node positive stage II breast cancer were randomised to four groups after radical mastectomy and axillary evacuation: (1) Postoperative radiotherapy, (2) Adjuvant chemotherapy with eight courses of CAFt (cyclophosphamide 500 mg m-2 + doxorubicin 40 mg/m-2 + ftorafur 20 mg kg-1 orally day 1-14) every fourth week, (3) Postoperative radiotherapy and adjuvant chemotherapy and (4) postoperative radiation, adjuvant chemotherapy and tamoxifen 40 mg daily for 2 years. Thirty-two per cent of the patients discontinued treatment due to GI-toxicity, while 26% required dose reductions due to leukopenia. Radiation pneumonitis was more frequent after the combination of postoperative radiotherapy with chemotherapy. There was a better relapse-free survival in the groups receiving chemotherapy compared to radiotherapy alone (P = 0.05), which was highly significant in a multivariate Cox analysis (P = 0.004). No significant survival differences were seen. Tamoxifen had no clear overall effect but there were better relapse-free (P = 0.04) and overall (P = 0.004) survival with tamoxifen in estrogen receptor positive patients, while estrogen receptor negative patients had a somewhat poorer survival (P = 0.07) after tamoxifen. Local control was better (NS) after the combination (93%) radiotherapy and chemotherapy compared to either treatment alone (76% with radiotherapy and 74% with chemotherapy at 5 years).
Radiation therapy is an essential modality in the treatment of breast cancer. Addition of radiotherapy to surgery has significantly increased local control and survival rates of the disease. However, radiotherapy is also associated with side effects, such as tissue fibrosis or enhanced vascular morbidity. Modern radiotherapy strategies, such as intensity modulated radiotherapy (IMRT), can shorten the overall treatment time by integration of the additional tumor bed boost significantly. To what extent this might be possible without impairing treatment outcome and cosmetic results remains to be clarified.
The IMRT-MC2 study is a prospective, two armed, multicenter, randomized phase-III-trial comparing intensity modulated radiotherapy with integrated boost to conventional radiotherapy with consecutive boost in patients with breast cancer after breast conserving surgery. 502 patients will be recruited and randomized into two arms: patients in arm A will receive IMRT in 28 fractions delivering 50.4 Gy to the breast and 64.4 Gy to the tumor bed by integrated boost, while patients in arm B will receive conventional radiotherapy of the breast in 28 fractions to a dose of 50.4 Gy and consecutive boost in 8 fractions to a total dose of 66.4 Gy.
Primary objectives of the study are the evaluation of the cosmetic results 6 weeks and 2 years post treatment and the 2- and 5-year local recurrence rates for the two different radiotherapy strategies. Secondary objectives are long term overall survival, disease free survival and quality of life.
ClinicalTrials.gov Protocol ID: NCT01322854.
Triethylene thiophosphoramide (Thio-TEPA) as an adjuvant to radical mastectomy for the treatment of carcinoma of the breast has been shown to be effective in reducing tumour recurrences. In many centres radiotherapy is considered valuable in breast cancer treatment, and in the minds of many there has existed the question of the safety of giving triethylene thiophosphoramide, a radiomimetic drug, at the time of surgery to the patient destined to receive post-operative radiotherapy. Fears had been expressed that the additive effects of triethylene thiophosphoramide and radiotherapy would result in serious complications and preclude the use of this valuable drug.
A total of 70 patients with breast cancer were treated by radical mastectomy and administration of triethylene thiophosphoramide. Most patients received postoperative radiotherapy. Results of this study showed that the benefit of adjuvant chemotherapy with triethylene thiophosphoramide need not be withheld and that the drug may be administered with safety to the patient with breast carcinoma for whom radical mastectomy and postoperative radiotherapy are planned.
Radiation therapy after lumpectomy is a standard part of breast conserving therapy for invasive breast carcinoma. The most frequently used schedule worldwide is 60 Gy in 30 fractions in 6 weeks, a time commitment that sporadically may dissuade some otherwise eligible women from undertaking treatment. The purpose and primary endpoint of this perspective study is to evaluate feasibility and short-term late toxicity in a hypofractionated whole breast irradiation schedule.
Between February and October 2008 we treated 65 consecutive patients with operable invasive early-stage breast cancer with a hypofractionated schedule of external beam radiation therapy. All patients were assigned to 39 Gy in 13 fractions in 3 weeks to the whole breast plus a concomitant weekly boost dose to the lumpectomy cavity of 3 Gy in 3 fractions.
All the patients had achieved a median follow up of 24 months (range 21-29 months). At the end of treatment 52% presented grade 0 acute toxicity 39% had grade 1 and 9% had grade 2. At 6 months with all the patients assessed there were 34% case of grade 1 subacute toxicity and 6% of grade 2. At 12 months 43% and 3% of patients presented with clinical grade 1 and grade 2 fibrosis respectively and 5% presented grade 1 hyperpigmentation. The remaining patients were free of side effects. At 24 months, with 56 assessed, just 2 patients (3%) showed grade 2 of late fibrosis.
The clinical results observed showed a reasonably good feasibility of the accelerated hypofractionated schedule in terms of acute, subacute and short-term late toxicity. This useful 13 fractions with a concomitant boost schedule seems, in selected patients, a biologically acceptable alternative to the traditional 30 days regime.
Patients have reported late effects and symptom-related bother following postoperative radiotherapy for prostate cancer.
Patients treated with postoperative radiotherapy were surveyed at a median 56 months after radiotherapy using the Prostate Cancer Radiation Therapy instrument. A retrospective review was undertaken to obtain Radiation Therapy Oncology Group-Late Effects Normal Tissue (RTOG-LENT) toxicity scores at baseline and during follow-up.
Survey response was 64.5%. Median prostate bed radiation dose was 66 Gy given at a median 14 months after surgery. Adjuvant hormone therapy was given for 2 to 3 years to 40 patients; 22 received salvage therapy.
PCRT impairment subscales were reported as mild for gastrointestinal dysfunction, moderate for genitourinary dysfunction and marked for sexual dysfunction. The use of one or more incontinence pads daily was reported by 25.6% and was similar to 23% use reported at baseline. Frequent or worse urinary frequency or hematuria was reported by 4.8%, and by 8.4% of respondents for bowel dysfunction. Moderate to severe disruption from bowel and bladder dysfunction was reported by up to 5.4% and 2.4% of respondents, respectively.
Erectile function was described as poor to none in 88.3% of respondents, and dissatisfaction with sexual functioning was reported by 42.7%. Counselling or treatment was offered to 59% of those followed.
Combined surgery and postoperative radiotherapy are associated with low and moderate rates of bowel and bladder dysfunction respectively, with low reported bother. High levels of sexual dysfunction and bother are seen following combined therapy. More effective pre- and post-treatment counselling are required, along with research into more effective prevention and treatment strategies.
Trastuzumab is used as adjuvant treatment in patients with HER2-positive breast cancers and has been shown to reduce the chance of recurrence by up to 50%. However, experience with it given with radiotherapy is limited and there is in vitro evidence of a radiosensiti-sation effect. We describe the first case of trastuzumab-associated radiation-induced myelitis.
This patient received a calculated dose of 28 Gy to the spinal cord when receiving adjuvant radiotherapy to the chest wall and supraclavicular and axillary lymph nodes. This is well below the accepted radiation tolerance of the spinal cord (50-60 Gy) but she developed radiation-induced myelitis of her spinal cord with characteristic magnetic resonance imaging changes. We postulate that trastuzu-mab given concurrently with radiation may have acted as a radiosensitiser and that normal repair mechanisms in the acute stage were affected by trastuzumab blockage of epidermal growth factor receptors, resulting in demy-elination at a lower dose of radiation than normally seen.
Concomitant radiotherapy and adjuvant trastuzumab treatment should be given with caution and consideration made of delaying trastuzumab until after radiotherapy has been completed. As longer-term data become available for patients who received trastuzumab and radiation, it will become clearer whether there is a significant interaction on organs such as the heart and spinal cord in the radiation field.
Breast cancer; Chemotherapy; External beam radiotherapy; Trastuzumab; Radiosensitisation
Between May 1973 and December 1980 there were 76 patients (78 breasts) with clinical stage I or II breast carcinoma treated by biopsy and definitive radiotherapy at Stanford University Medical Center. Local-regional control has been achieved thus far in 76 of 78 cases (97 percent) with a median follow-up time of 26 months. Transient lymphedema of the breast, arm edema and breast fibrosis were the most commonly noted complications. The cosmetic result was analyzed and scored as excellent in 78 percent, satisfactory in 18 percent and unsatisfactory in 4 percent. The three unsatisfactory results occurred in patients in whom severe fibrosis developed as a result of suboptimal radiation techniques. Interdisciplinary cooperation among surgical, medical and radiation oncologists is important. The 97 percent local-regional control and the 96 percent excellent-to-satisfactory results support the use of primary radiotherapy in early stage breast carcinoma.
Radiotherapy outcomes might be further improved by a greater understanding of the individual variations in normal tissue reactions that determine tolerance. Most published studies on radiation toxicity have been performed retrospectively. Our prospective study was launched in 1996 to measure the in vitro radiosensitivity of peripheral blood lymphocytes before treatment with radical radiotherapy in patients with breast cancer, and to assess the early and the late radiation skin side effects in the same group of patients. We prospectively recruited consecutive breast cancer patients receiving radiation therapy after breast surgery. To evaluate whether early and late side effects of radiotherapy can be predicted by the assay, a study was conducted of the association between the results of in vitro radiosensitivity tests and acute and late adverse radiation effects.
Intrinsic molecular radiosensitivity was measured by using an initial radiation-induced DNA damage assay on lymphocytes obtained from breast cancer patients before radiotherapy. Acute reactions were assessed in 108 of these patients on the last treatment day. Late morbidity was assessed after 7 years of follow-up in some of these patients. The Radiation Therapy Oncology Group (RTOG) morbidity score system was used for both assessments.
Radiosensitivity values obtained using the in vitro test showed no relation with the acute or late adverse skin reactions observed. There was no evidence of a relation between acute and late normal tissue reactions assessed in the same patients. A positive relation was found between the treatment volume and both early and late side effects.
After radiation treatment, a number of cells containing major changes can have a long survival and disappear very slowly, becoming a chronic focus of immunological system stimulation. This stimulation can produce, in a stochastic manner, late radiation-related adverse effects of varying severity. Further research is warranted to identify the major determinants of normal tissue radiation response to make it possible to individualize treatments and improve the outcome of radiotherapy in cancer patients.
Locoregional control of breast cancer is the shared domain and responsibility of surgeons and radiation oncologists. Because surgeons are often the first providers to discuss locoregional control and recurrence risks with patients and because they serve in a key gatekeeping role as referring providers for radiation therapy, a sophisticated understanding of the evidence regarding radiotherapy in breast cancer management is essential for the practicing surgeon. This paper synthesizes the complex and evolving evidence regarding the role of radiation therapy after mastectomy. Although substantial evidence indicates that radiation therapy can reduce the risk of locoregional failure after mastectomy (with a relative reduction of risk of approximately two-thirds), debate persists regarding the specific subgroups who have sufficient risks of residual microscopic locoregional disease after mastectomy to warrant treatment with radiation. This paper reviews the evidence available to guide appropriate referral and patient decision making, with special attention to areas of controversy, including patients with limited nodal disease, those with large tumors but negative nodes, node-negative patients with high risk features, patients who have received systemic chemotherapy in the neoadjuvant setting, and patients who may wish to integrate radiation therapy with breast reconstruction surgery.
Breast cancer remains the most common malignancy in women. Since the late 1980s, significant advances have been made in the treatment of this cancer. Those advances, particularly the ones in the adjuvant setting, have led to declines in the mortality associated with breast cancer. But another result has been treatments that are more complex and that potentially carry more toxicity. One key toxicity related to the adjuvant therapy of breast cancer is cardiac toxicity. Some of the agents commonly used for the treatment of breast cancer, including anthracyclines, trastuzumab, and possibly even aromatase inhibitors, have been associated with cardiac toxicity. The present article reviews the current understanding of cardiac toxicity risk and strategies to minimize cardiac morbidity associated with cytotoxic chemotherapy, trastuzumab therapy, and hormonal therapy with aromatase inhibitors for early-stage breast cancer.
Anthracyclines; trastuzumab; aromatase inhibitors; cardiac toxicity
To quantify the multi-institutional and multi-observer variability of target and organ-at-risk (OAR) delineation for breast-cancer radiotherapy (RT), and its dosimetric impacts, as the first step of a RTOG effort to establish a breast cancer atlas.
Methods and Materials
Nine radiation oncologists specializing in breast RT from eight institutions independently delineated targets (e.g., lumpectomy cavity, boost planning target volume, breast, supraclavicular, axillary and internal mammary nodes, and chest wall) and OARs (e.g., heart, lung) on the same CT images of three representative patients with breast cancer. Inter-observer differences in structure delineation were quantified with regard to volume, distance between centers of mass, percent overlap, and average surface distance. The mean, median and standard deviation for these quantities were calculated for all possible combinations. To asses the impact of these variations on treatment planning, representative dosimetric plans based on observer-specific contours were generated.
The variability in contouring the targets and OARs between the institutions/observers was substantial. The structure overlaps were as low as 10% and the volume variations had standard deviations up to 60%. The large variability was related both to differences in opinion regarding target and OAR boundaries as well as approach to incorporation of setup uncertainty and dosimetric limitations in target delineation. These inter-observer differences result in substantial variations in dosimetric planning for breast RT.
The differences in target and OAR delineation for breast irradiation between institutions/observers appear to be clinically and dosimetrically significant. A systematic consensus is highly desirable, particularly in the era of IMRT/IGRT.
breast radiotherapy; breast treatment planning; breast delineation; breast cancer
Background and purpose
Several small studies have reported associations between TGFB1 single nucleotide polymorphisms (SNPs), considered to increase secretion of TGF-β1, and greater than 3-fold increases in incidence of fibrosis – an indicator of late toxicity after radiotherapy in breast cancer patients.
Materials and methods
Two SNPs in TGFB1, C-509T (rs1800469) and L10P (rs1800470), were genotyped in 778 breast cancer patients who had received radiotherapy to the breast. Late radiotherapy toxicity was assessed two years after radiotherapy using a validated photographic technique, clinical assessment and patient questionnaires.
On photographic assessment, 210 (27%) patients showed some degree of breast shrinkage, whilst 45 (6%) patients showed marked breast shrinkage. There was no significant association of genotype at either of the TGFB1 SNPs with any measure of late radiation toxicity.
This adequately powered trial failed to confirm previously reported increases in fibrosis with TGFB1 genotype – any increase greater than 1.36 can be excluded with 95% confidence. Similar frequent failures to replicate associations with candidate genes have been resolved using genome-wide association scans: this methodology detects common, low risk alleles but requires even larger patient numbers for adequate statistical power.
Radiotherapy; Breast; Genetics; TGFB1; Breast cancer
Multiple adjuvant regimens are used for HER2+ breast cancer, but experience in routine practice is not reported. We evaluated whether oncologists’ perceptions of these regimens matches clinical experience. We surveyed Wisconsin medical oncologists throughout the state regarding factors impacting selection of TCH (docetaxel, carboplatin, trastuzumab) or anthracycline-based therapy. We also reviewed 200 cases of HER2+ breast cancer treated at the University of Wisconsin and the Marshfield Clinic and collected data on patient and tumor characteristics, chemotherapy regimen, and toxicities. Two-thirds of surveyed oncologists prefer anthracycline-based therapy, particularly for node-positive cancers. However, TCH was preferred for early stage (T1a-bN0) tumors. Half of oncologists use prophylactic G-CSF with TCH. In the 200 cases reviewed at our centers, acute toxicity occurred more frequently with TCH. There were fewer dose modifications or delays for AC-TH (doxorubicin, cyclophosphamide, paclitaxel, trastuzumab) than TCH (31% vs. 47%, p=0.07), possibly due to higher use of prophylactic G-CSF with AC-TH (77% vs. 34% with TCH, p<0.001). Fifteen patients received prophylactic G-CSF during TCH; none developed neutropenic fever. In contrast, 25% developed neutropenic fever during TCH without G-CSF. There were modest declines in median left ventricular ejection fraction reaching 9% with AC-TH and 3% with TCH at 12 months, but early cessation of trastuzumab was similar for both regimens. We conclude that TCH and AC-TH are common adjuvant regimens used for HER2+ breast cancer. The preference of TCH for early-stage disease and anthracycline-based therapy for node-positive disease suggests that many oncologists perceive that TCH is safer and AC-TH more effective. Myelosuppression from TCH is greater than AC-TH, but can be mitigated with routine G-CSF.
ErbB2; chemotherapy; trastuzumab; neutropenic fever; myelosuppression; cardiotoxicity
To explore if the addition of adjuvant chemotherapy with paclitaxel and carboplatin to radiotherapy confers an advantage for overall survival (OAS), and progression free survival (PFS); to assess the incidence of relapses over standard pelvic radiotherapy; and to evaluate the related toxicity in high-risk stage I-II endometrial carcinoma
Medical records were reviewed to identify high-risk stage I-II endometrial carcinoma cases treated in the Clinical Oncology and Nuclear Medicine department between 2002 and 2008 with adjuvant radiotherapy alone (arm I) (57 patients) or with sequential carboplatin (AUC5-6) and paclitaxel (135−175 mg/m2) with radiotherapy (arm II) (51 patients). Radiotherapy was performed through the four-field box technique at doses of 45−50 Gy (1.8 Gy/day × 5 days/week).
The toxicity was manageable and predominantly hematologic with a grade 3 neutropenia and thrombocytopenia in 9.8% and 6% of the patients in arm I and arm II, respectively, without febrile neutropenia. All patients experienced hair loss. Chemoradiotherapy arm was associated with a lower incidence rate of relapse (9.8% vs. 22.7%). After a median follow-up period of 48 months, the 5-year OAS and PFS rates for chemoradiotherapy-treated patients were significantly more favorable than those who did not receive chemotherapy (P=0.02 and 0.03, respectively). In arm I, the OAS and PFS rates were 73.7% and 66.7% compared with those in arm II, whose rates were 90.2% and 84.3%.
Adjuvant chemoradiation with paclitaxel and carboplatin improved the survival rates and decreased the recurrence rates in patients with high-risk stage I-II endometrial carcinoma. Chemotherapy was associated with an acceptable rate of toxicity. However, a prospective study with a larger number of patients is needed to define a standard adjuvant treatment for high-risk stage I-II endometrial carcinoma.
stage I-II high-risk endometrial cancer; adjuvant radiotherapy; adjuvant sequential chemoradiotherapy
Immediate breast reconstruction after mastectomy and delayed breast reconstruction with post-supplementary treatment are the two types of breast reconstruction currently performed when treating breast cancer. Post-mastectomy radiation therapy (PMRT) not only reduces local recurrence but also improves overall survival. However, the complications and survival rates associated with PMRT need to be clear when determining the timing of breast reconstruction. Accordingly, we investigated the optimal timing of breast reconstruction by observing patients who underwent mastectomy followed by PMRT, based on their overall health and aesthetic satisfaction.
We retrospectively reviewed 21 patients who underwent breast reconstruction with PMRT between November 2004 and November 2010. We collected data regarding the various methods of mastectomy, and the modality of adjuvant therapy, such as chemotherapy, hormone therapy, and radiotherapy. Telephone interviews were conducted to study the general and aesthetic satisfaction.
Patients who received PMRT after breast reconstruction showed a greater complication rate than those undergoing breast reconstruction after PMRT (P=0.02). Aesthetic satisfaction was significantly higher in the groups undergoing breast reconstruction after PMRT (P=0.03). Patients who underwent breast reconstruction before PMRT developed complications more frequently, but they expressed greater aesthetic satisfaction with the treatment.
It is recommended that the complication rates and aesthetic satisfaction after breast reconstruction be carefully considered when determining the optimal timing for radiotherapy.
Breast; Mastectomy; Radiotherapy
Breast cancer patients of an advanced age will suffer from ailments related to both senescence and cancer. Some will have been denied access to screening programmes and will present with an advanced disease. Many will need the expertise of the geriatrician and the oncologist who will participate in specific case discussions to look at social and medical issues that will affect the treatment plan (with questions regarding surgery, radiation, drug therapy, rehabilitation, supportive care, and palliative care often intertwined). This paper reviews recommendations by the International Society of Geriatric Oncology (SIOG) task force which recently assessed the available evidence on breast cancer in elderly individuals, and provided evidence-based recommendations for the diagnosis and treatment of breast cancer in such individuals. Recommendations on the topics of screening, surgery, radiotherapy, (neo)adjuvant hormone treatment, and chemotherapy, and on metastatic disease have been given. Oncologists are now learning to take into account the physiological age of their patient, which is the reflection of a normal and sometimes abnormally accelerated loss of body reserves which is certainly related to chronological age but not precisely dictated by it. Understanding the biology of breast cancer will allow to optimally adapt the treatment of the elderly patient.
Breast cancer; Elderly; Geriatric assessment; Creatinine clearance; Comorbidity
Concurrent chemoradiotherapy (CCRT) after breast surgery was investigated by few authors and remains controversial, because of concerns of toxicity with taxanes/anthracyclines and radiation. This treatment is not standard and is more commonly used for locally advanced breast cancer. The aim of our study was to evaluate the efficacy and safety of the concomitant use of anthracycline with radiotherapy (RT).
Four hundred women having operable breast cancer, treated by adjuvant chemotherapy (CT) and RT in concomitant way between January 2001 and December 2003, were included in this retrospective cohort study. The study compares 2 adjuvant treatments using CCRT, the first with anthracycline (group A) and the second with CMF (group B). The CT treatment was repeated every 21 days for 6 courses and the total delivered dose of RT was 50 Gy, divided as 2 Gy daily fractions. Locoregional recurrence free (LRFS), event free (EFS), and overall survivals (OS) were estimated by the Kaplan-Meier method. The log-rank test was used to compare survival events. Multivariate Cox-regression was used to evaluate the relationship between patient characteristics, treatment and survival.
In the 2 groups (A+B) (n = 400; 249 in group A and 151 in group B), the median follow-up period was 74.5 months. At 5 years, the isolated LRFS was significantly higher in group A compared to group B (98.7% vs 95.3%; hazard ratio [HR] = 0.258; 95% CI, 0.067 to 0.997; log-rank P = .034). In addition, the use of anthracycline regimens was associated with a higher rate of 5 years EFS (80.4% vs 75.1%; HR = 0.665; 95% CI, 0.455 to 1.016; log-rank P = .057). The 5 years OS was 83.2% and 79.2% in the anthracycline and CMF groups, respectively (HR = 0.708; 95% CI, 0.455 to 1.128; log-rank P = .143). Multivariate analysis confirmed the positive effect of anthracycline regimens on LRFS (HR = 0.347; 95% CI, 0.114 to 1.053; log-rank P = .062), EFS (HR = 0.539; 95% CI, 0.344 to 0.846; P = 0.012), and OS (HR = 0.63; 95% CI, 0.401 to 0.991; P = .046). LRFS, EFS and OS were significantly higher in the anthracycline group where the patients (n = 288) received more than 1 cycle of concurrent CT (P = .038, P = .026 and P = .038, respectively). LRFS and EFS were significantly higher in the anthracycline group within the BCT subgroup (P = .049 and P = .04, respectively). There were more hematologic, and more grade 2/3/4 skin toxicity in the anthracycline group.
After mastectomy or BCT, the adjuvant treatment based on anthracycline and concurrent RT reduced breast cancer relapse rate, and significantly improved LRFS, EFS and OS in the patients receiving more than 1 cycle of concurrent CT. There were more hematologic and non hematologic toxicities in the anthracycline group.
Breast cancer is the most frequent cancer among women and the leading cause of death among middle-aged women. Early detection by mammography screening and improvement of therapeutic options have increased breast cancer survival rates, with the consequence that late side effects of cancer treatment become increasingly important. In particular, patients treated with adjuvant chemotherapy regimens, commonly including alkylating agents and anthracyclines, are at increased risk of developing leukemia, further enhanced by the use of radiotherapy. In the last few years also the use of growth factors seems to increase the risk of secondary leukemia. The purpose of this review is to update epidemiology of therapy-related myeloid neoplasms occurring in breast cancer patients.