Acute Toxicity of High-Dose-Rate Intracavitary Brachytherapy With the MammoSite Applicator in Patients With Early-Stage Breast Cancer

Background: Intracavitary brachytherapy with the MammoSite applicator as the sole radiation treatment in breast-conserving therapy is an option for women with early-stage breast cancer; we evaluated the acute toxicities associated with this treatment method.Methods: Thirty-one patients with 32 stage I or II breast carcinomas underwent breast-conserving therapy, which included lumpectomy with negative margins, sentinel node biopsy, or axillary dissection, followed by brachytherapy with the MammoSite applicator. Acute radiation skin complications were graded on the day of radiotherapy completion and at weeks 2, 4, 6, and 12 after radiation treatment. Cosmesis was graded on the Harvard Scale at all follow-ups.Results: The median follow-up was 11 months (range, 4–15 months). Twenty-seven of the 31 patients were treated with the device as the sole method of radiotherapy. No acute toxicities occurred during the 5 days of treatment. Nineteen patients (68%) had no to mild acute skin reactions, and 25% developed bright erythema and patchy moist desquamation. Two patients (7%) developed confluent moist desquamation within the first 4 weeks (grade 3); this healed by week 12. All skin reactions were localized to the area overlying the balloon. Sixteen percent (5 of 32) of all breasts with implants developed infection. Cosmesis was good to excellent in 86% of cases.Conclusions: Most acute skin toxicities were mild. Our infection rate was higher than in prior studies that used interstitial brachytherapy. Cosmesis was good to excellent in most patients. Breast brachytherapy with the MammoSite catheter was well tolerated; further investigations of breast brachytherapy with this system are warranted.     

Avoidance of Adjuvant Radiotherapy in Selected Patients With Invasive Breast Cancer

Background: Current standard therapy for invasive breast carcinoma is mastectomy or breast conservation with adjuvant radiation. Data from randomized trials suggest no advantage for radiotherapy after lumpectomy in highly selected patients. Selective radiotherapy would make contemporary breast cancer therapy more rational with decreased morbidity and expense.Methods: A total of 163 patients were treated by breast conservation without adjuvant radiation between 1978 and June 2003. They declined radiation after discussion or had medical contraindications. The great majority were postmenopausal and had lower-grade T1 tumors with resection margins 1 cm and no nodal metastases. The goal was to identify patients with favorable prognostic features for omission of postsurgical irradiation without impaired local recurrence or survival.Results: Twenty patients (12%) had local recurrences; 17 (10%) were invasive, and 3 (2%) were ductal carcinoma-in-situ. An ideal patient subgroup >50 years of age with grade 1 or 2 cancers 1.5 cm in diameter and with surgical margins 1 cm was empirically defined. Of 80 such patients, 5 (6%) had local recurrence; 3 (3.5%) were invasive, and 2 (2.5%) were ductal carcinoma-in-situ.Conclusions: A defined ideal subset of older breast cancer patients with smaller, lower-grade cancers and adequate excision margins can be treated with lumpectomy without irradiation and with minimal local recurrence.     

Local recurrence in lumpectomy patients after imprint cytology margin evaluation

BACKGROUND: This is a follow-up study to our previously reported data on local recurrence rates in patients whose lumpectomy margins were evaluated by intraoperative imprint cytology (IIC(M)). The purpose of this study was to compare local recurrence rates for patients whose lumpectomy margins were evaluated with IIC(M) with local recurrence rates of those not evaluated by IIC(M). METHODS: A total of 1713 patients underwent lumpectomy treatment for breast cancer from 1988 to 2001 were prospectively entered into a computerized database and subsequently included in this study. Of the patients, 520 (group 1) had their surgery performed at an outside institution where conventional margin analysis was performed. Another 1193 (group 2) had their surgery performed at our institution where margins were evaluated by IIC(M). For each histologic type and for the overall sample, probabilities of recurrence with time were estimated using the method of Kaplan and Meier. RESULTS: IIC(M) overcomes sampling error inherent in the frozen section analysis and results in a diminished incidence of overall 5-year local recurrence from 8.8% to 2.8% (P <0.0001). The recurrence rates for each respective histologic subtype are reported for both absolute recurrences and probability of recurrence with time. CONCLUSIONS: IIC(M) provides an accurate evaluation of lumpectomy margins for patients undergoing breast-conservation treatment. IIC(M) was associated with an overall lower local recurrence rate. This series defined the utility of intraoperative imprint cytology for evaluation of margins in patients undergoing breast-conservation treatment.     

Intensity modulation to improve dose uniformity with tangential breast radiotherapy: initial clinical experience

Purpose: We present a new technique to improve dose uniformity and potentially reduce acute toxicity with tangential whole-breast radiotherapy (RT) using intensity-modulated radiation therapy (IMRT). The technique of multiple static multileaf collimator (sMLC) segments was used to facilitate IMRT.

Methods and Materials: Ten patients with early-stage breast cancer underwent treatment planning for whole-breast RT using a new method of IMRT. The three-dimensional (3D) dose distribution was first calculated for equally weighted, open tangential fields (i.e., no blocks, no wedges). Dose calculation was corrected for density effects with the pencil-beam superposition algorithm. Separate MLC segments were constructed to conform to the beam’s-eye-view projections of the 3D isodose surfaces in 5% increments, ranging from the 120% to 100% isodose surface. Medial and lateral MLC segments that conformed to the lung tissue in the fields were added to reduce transmission. Using the beam-weight optimization utility of the 3D treatment planning system, the sMLC segment weights were then determined to deliver the most uniform dose to 100 reference points that were uniformly distributed throughout the breast. The accuracy of the dose calculation and resultant IMRT delivery was verified with film dosimetry performed on an anthropomorphic phantom. For each patient, the dosimetric uniformity within the breast tissue was evaluated for IMRT and two other treatment techniques. The first technique modeled conventional practice where wedges were derived manually without consideration of inhomogeneity effects (or density correction). A recalculation was performed with density correction to represent the actual dose delivered. In the second technique, the wedges were optimized using the same beam-weight optimization utility as the IMRT plan and included density correction. All dose calculations were based on the pencil-beam superposition algorithm.

Results: For the sMLC technique, treatment planning required approximately 60 min. Treatment delivery (including patient setup) required approximately 8–10 min. Film dosimetry measurements performed on an anthropomorphic phantom generally agreed with calculations to within ± 3%. Compared to the wedge techniques, IMRT with sMLC segments resulted in smaller “hot spots” and a lower maximum dose, while maintaining similar coverage of the treatment volume. A median of only 0.1% of the treatment volume received ≥ 110% of the prescribed dose when using IMRT versus 10% with standard wedges. A total of 6–8 segments were required with the majority of the dose delivered via the open segments. The addition of the lung-block segments to IMRT was of significant benefit for patients with a greater proportion of lung parenchyma within the irradiated volume. Since August 1999, 32 patients have been treated in the clinic with the IMRT technique. No patient experienced RTOG grade III or greater acute skin toxicity.

Conclusion: The use of intensity modulation with an sMLC technique for tangential breast RT is an efficient and effective method for achieving uniform dose throughout the breast. It is dosimetrically superior to the treatment techniques that employ only wedges. Preliminary findings reveal minimal or no acute skin reactions for patients with various breast sizes.     

Factors predicting residual disease on re-excision after breast conserving surgery

IntroductionBreast conserving surgery is the standard of care for early breast cancer, however in a quarter of patients, satisfactory margins are not achieved, usually leading to re-excision. Residual disease is found in less than half of these re-excisions, leading to increased morbidity, poorer cosmesis and increased cost, possibly with no oncological benefit. Our study aimed to identify a group of patients with unsatisfactory margins but a low risk of residual disease, who may be able to avoid re-excision.Methods and materialsAll patients from our unit undergoing re-excision for unsatisfactory margins after breast conserving surgery between January 2013 and October 2019 were identified. Pathological factors predicting residual disease were investigated using univariable and multivariable analysis.Results220 patients were included. 90 (41 %) had residual disease. Residual disease was more likely in those having mastectomy than cavity shaves (61 % vs 32 %, p < 0.0001). Residual disease increased in a linear fashion with number of involved margins and with increasing tumour size. Tumour size <20 mm (p = 0.045), a pathological to radiological tumour size ratio less than 1.5 (p < 0.0001) and disease-free cavity shaves taken at initial surgery (p = 0.041) were all independent predictors of a low chance of residual disease on multivariable analysis. Patients with all three factors had a 14 % chance of residual disease.ConclusionsMore than half of patients undergo potentially unnecessary re-excision, and patients with small, radiologically obvious tumours are less likely to have residual disease. The decision on re-excision should include these factors in addition to the margin status.     

Molecular evidence demonstrating local treatment failure is the source of distant metastases in some patients treated for breast cancer

PURPOSE: To examine the clonality relationships among initial invasive breast carcinoma (IBC), ipsilateral breast failure (IBF), and distant metastasis (DM) to determine the effect of local tumor recurrence on the development of DMs. METHODS AND MATERIALS: A total of 18 patients treated with breast-conserving therapy who developed an IBF followed by DMs were studied using a 20 informative-marker, polymerase chain reaction-based allelic imbalance clonality assay. RESULTS: Four relationships were identified. First, in 7 cases, the IBF and DMs were clonally related to the initial IBC as one progressively genetic unstable process. Second, in 3 cases, the IBF and DMs were each clonally related to the IBC but clonally distinct from each other. Third, in 3 cases, the IBC and the IBF were clonally related and the DMs were clonally related to the IBFs, with a weak relationship to the initial IBC. Finally, in 5 cases, the IBF was clonally distinct from the initial IBC (new second primary) and the DMs were clonally related to the IBF and clonally distinct from the initial IBC. CONCLUSION: These findings provide molecular evidence demonstrating that some DMs can directly develop from IBFs and support the importance of local tumor control in the overall treatment of breast cancer patients.     

Palliative Local Surgery for Locally Advanced Breast Cancer Depending on Hormone Receptor Status in Elderly Patients

Background

Many elderly breast cancer patients might just receive palliative local surgery, especially those with locally advanced breast cancer (LABC). However, palliative tumor removal might lead to perioperative residual tumor growth. In this study, we aimed to determine the survival effect of palliative local surgery without definitive axillary surgery for LABC in elderly patients.

Lumpectomy margins are affected by tumor size and histologic subtype but not by biopsy technique

OBJECTIVE: The effect of the type of biopsy (needle vs. excisional) on lumpectomy margin status has not been well established. The objective of this study was to determine whether needle biopsy is associated with a higher positive margin rate at time of lumpectomy. METHODS: We evaluated this hypothesis in the setting of a prospective multi-institutional study. A total of 3975 patients were enrolled in the University of Louisville Breast Cancer Sentinel Lymph Node Study from May 7, 1998 to June 3, 2003. Patients who underwent lumpectomy at the time of their sentinel lymph node biopsy were the focus of this analysis. Patients with clinical stage T1 N0 and T2 N0breast cancer were eligible; 29 patients were found to have T3 tumors on final pathology. Pathologists at each institution defined margin positivity, and tumor at the inked margin of resection was the study guideline. RESULTS: Median patient age was 59 years, and median tumor size was 1.5 cm. A total of 2658 patients underwent lumpectomy with the following results. The cancer of 1515 patients was diagnosed by fine-needle or core-needle biopsy and of 821 patients was diagnosed by excisional biopsy; in 322 patients the method of diagnosis was unknown. The type of previous biopsy did not significantly affect the positive-margin rate at the time of lumpectomy (13.3% vs. 11.0% for needle and excisional biopsy, respectively, P = 0.107). However, patients with larger tumors were more often found to have a positive margin (11.4% vs. 13.9% vs. 27.6% for T1, T2, and T3 tumors, respectively; P = 0.010). No difference was found in margin status after excision of palpable versus nonpalpable tumors (10.6% vs. 10.9%, respectively, P = 0.743). Histologic subtype, however, did affect margin status (15.8% vs. 9.8% positive margins for lobular vs. ductal type, respectively, P = 0.003). CONCLUSIONS: In this multi-institutional study, increasing tumor size and lobular histologic subtype were associated with a greater likelihood of a positive margin. The type of biopsy, needle or excisional, had no effect on the ability to achieve negative margins.     

Analysis of residual cancer after diagnostic breast biopsy: An argument for fine-needle aspiration cytology

Background: Diagnostic breast biopsy (DxBx) requires an effective strategy for strategy for successful treatment of breast cancer by lumpectomy or mastectomy. Clearance of margins is required to achieve local control. Methods: We reviewed 844 malignant diagnostic biopsies. The strategy was to perform DxBx on all nonpalpable lesions and fine-needle aspiration (FNA) on all palpable lesions. When FNA was equivocal, DxBx was performed. After positive DxBx, either the biopsy cavity or FNA-positive breast mass was excised, and margins were documented with touch preparation cytology analysis (TPC) and frozen section (FS) as necessary to achieve negative margins. Results: Ourside institutions referred 430 excisional biopsies. Two hundred twenty-five (52.3%) were found to have residual cancer at surgical excision. Our institution performed 414 biopsies: 169 were performed on nonpalpable lesions in which 58% had residual tumor at resection; 245 were diagnosed by FNA of palpable lesions. Residual disease was found in 12 (5%). Conclusions: Of patients who undergo DxBx, >50% have residual breast cancer. It is recommended that (a) FNA be performed on all palpable masses or DxBx of nonpalpable masses; when cancer is diagnosed, proceed to surgical excision. (b) When lumpectomy is the option, margins should be reexcised and intraoperatively evaluated with TPC and FS at the time of axillary dissection.     

Breast conservation for male breast carcinoma

Male breast cancer in general is treated by modified radical mastectomy. Data have emerged supporting the replacement of the axillary lymph node dissection by a sentinel lymph node biopsy in the male patient with breast carcinoma. Local therapy in the breast continues to be primarily mastectomy. The reasons suggested for this include the central location of many of the male breast tumors and the paucity of breast tissue. Our experience with breast conservation over the last decade in male breast carcinoma and a review of the literature is outlined here. Between 1996 and 2006, seven men underwent breast conservation for breast carcinoma and to date with a median follow-up of 67 months, there have been no local recurrences. Breast carcinoma in males can be treated with breast conservation with acceptable local recurrence. Breast-conserving surgery in male breast cancer patients should be considered an option in patients without overt nipple/areolar involvement.