BackgroundThe purpose of this consensus guideline is to outline recommendations for genetic testing that medical professionals can use to assess hereditary risk for breast cancer.MethodsLiterature review included large datasets, basic and clinical science publications, and recent updated national guidelines. Genetic testing to assess hereditary risk of cancer is a complex, broad, and dynamic area of medical research. The dominant focus of this guideline is limited in scope to breast cancer.ResultsThere is a lack of consensus among experts regarding which genes among many should be tested in different clinical scenarios. There is also variation in the degree of consensus regarding the understanding of risk and appropriate clinical management of mutations in many genes.ConclusionsGenetic testing should be made available to all patients with a personal history of breast cancer. Recent data are reviewed that support genetic testing being offered to each patient with breast cancer (newly diagnosed or with a personal history). If genetic testing is performed, such testing should include BRCA1/BRCA2 and PALB2, with other genes as appropriate for the clinical scenario and family history. For patients with newly diagnosed breast cancer, identification of a mutation may impact local treatment recommendations. Patients who had genetic testing previously may benefit from updated testing. Genetic testing should be made available to patients without a history of breast cancer who meet National Comprehensive Cancer Network guidelines. Finally, variants of uncertain significance are not clinically actionable and these patients should be managed based on their individual risk factors.
Preoperative or NST is emerging as an important initial strategy for the management of invasive breast cancer. From the surgeon's perspective, the primary goal of NST is to increase the resectability of locally advanced breast cancer, increase the feasibility of breast-conserving surgery and sentinel node biopsy, and decrease surgical morbidity. To ensure optimal patient selection and efficient patient care, the guideline recommends: (1) baseline breast and axillary imaging; (2) minimally invasive biopsies of breast and axillary lesions; (3) determination of tumor biomarkers; (4) systemic staging; (5) care coordination, including referrals to medical oncology, radiation oncology, plastic surgery, social work, and genetic counseling, if indicated; (6) initiation of NST; (7) post-NST breast and axillary imaging; and (8) decision for surgery based on extent of disease at presentation, patient choice, clinical response to NST, and genetic testing results, if performed.
Historically there has been a high rate of surgical interventions to obtain clear margins for breast cancer patients undergoing breast conserving local therapy. An intraoperative margin assessment tool (MarginProbe) has been approved for use in the US since 2013. This study is the first compilation of data from routine use of the device, to assess the impact of device utilization on re-excision rates. We present a retrospective, observational, review from groups of consecutive patients, before and after the implementation of intraoperative use of the device during lumpectomy procedures. Lesions were localized by standard methods. The intraoperative margin assessment device was used on all circumferential margins of the main specimen, but not on any additional shavings. A positive reading by the device led to an additional shaving of the corresponding cavity location. Specimens were also, when feasible, imaged intra-operatively by X-ray, and additional shavings were taken if needed based on clinical assessment. For each surgeon, historical re-excision rates were established based on a consecutive set of patients from a time period proximal to initiation of use of the device. From March 2013 to April 2014 the device was routinely used by 4 surgeons in 3 centers. In total, 165 cases lumpectomy cases were performed. Positive margins resulted in additional re-excision procedures in 9.7% (16/165) of the cases. The corresponding historical set from 2012 and 2013 consisted of 186 Lumpectomy cases, in which additional re-excision procedures were performed in 25.8% (48/186) of the cases. The reduction in the rate of re-excision procedures was significant 62% (P < 0.0001). Use of an intraoperative margin assessment device contributes to achieving clear margins and reducing re-excision procedures. As in some cases positive margins were found on shavings, future studies of interest may include an analysis of the effect of using the device on the shavings intra-operatively.
PurposeAccelerated partial breast irradiation (APBI) with balloon and strut adjusted volume implants (SAVI) show promising results with excellent tumor control and minimal toxicity. Knowing the factors that contribute to a high skin dose, rib dose, and D95 coverage may reduce toxicity, improve tumor control, and help properly predict patient outcomes following APBI.Methods and materialsA retrospective analysis of 594 patients treated with brachytherapy based APBI at a single institution from May 2008 to September 2014 was grouped by applicator subtype. Patients were treated to a total of 34 Gy (3.4 Gy x 10 fractions over 5 days delivered BID) targeting a planning target volume (PTV) 1.0 cm beyond the lumpectomy cavity using a high dose rate source.ResultsSAVI devices had the lowest statistically significant values of DmaxSkin (81.00 ± 29.83), highest values of D90 (101.50 ± 3.66), and D95 (96.09 ± 4.55). SAVI-mini devices had the lowest statistically significant values of DmaxRib (77.66 ± 32.92) and smallest V150 (18.01 ± 3.39). Multi-lumen balloons were able to obtain the smallest V200 (5.89 ± 2.21). Strut-based applicators were more likely to achieve a DmaxSkin and a DmaxRib less than or equal to 100 %. The effect of PTV on V150 showed a strong positive relationship (p < .001). PTV and DmaxSkin showed a weak negative relationship in multi-lumen applicators (p = .016) and SAVI-mini devices (p < .001). PTV and DmaxRib showed a weak negative relationship in multi-lumen applicators (p = .009), SAVI devices (p < .001), and SAVI-mini devices (p < .001).ConclusionPTV volume is strongly correlated with V150 in all devices and V200 in strut based devices. Larger PTV volumes result in greater V150 and V200, which could help predict potential risks for hotspots and resulting toxicities in these devices. PTV volume is also weakly negatively correlated with max skin dose and max rib dose, meaning that as the PTV volumes increase one can expect slightly smaller max skin and rib doses. Strut based applicators are significantly more effective in keeping skin and rib dose constraints under 125 and 100 % when compared to any balloon based applicator.
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