Reconstructive complications and early toxicity in breast cancer patients treated with proton-based postmastectomy radiation therapy

BackgroundPostmastectomy radiation therapy (PMRT) decreases the risk of locoregional recurrence and increases overall survival rates in patients with high-risk node positive breast cancer. While the number of breast cancer patients treated with proton-based PMRT has increased in recent years, there is limited data on the use of proton therapy in the postmastectomy with reconstruction setting. In this study, we compared acute toxicities and reconstructive complications in patients treated with proton-based and photon-based PMRT.MethodsA retrospective review of our institutional database was performed to identify breast cancer patients treated with mastectomy with implant or autologous reconstruction followed by PMRT from 2015 to 2020. Baseline clinical, disease, and treatment related factors were compared between the photon-based and proton-based PMRT groups. Early toxicity outcomes and reconstructive complications following PMRT were graded by the treating physician.ResultsA total of 11 patients treated with proton-based PMRT and 26 patients treated with photon-based PMRT were included with a median follow-up of 7.4 months (range, 0.7-33 months). Six patients (55%) in the proton group had a history of breast cancer (3 ipsilateral and 3 contralateral) and received previous RT 38 months ago (median, range 7-85). There was no significant difference in mean PMRT (p = 0.064) and boost dose (p = 0.608) between the two groups. Grade 2 skin toxicity was the most common acute toxicity in both groups (55% and 73% in the proton and photon group, respectively) (p = 0.077). Three patients (27%) in the proton group developed grade 3 skin toxicity. No Grade 4 acute toxicity was reported in either group. Reconstructive complications occurred in 4 patients (36%) in the proton group and 8 patients (31%) in photon group (p = 0.946).ConclusionsAcute skin toxicity remains the most frequent adverse event in both proton- and photon-based PMRT. In our study, reconstructive complications were not significantly higher in patients treated with proton- versus photon-based PMRT. Longer follow-up is warranted to assess late toxicities

Incidence of clinical lymphedema in breast cancer patients treated with adjuvant proton-based radiotherapy

Background: The purpose of this study was to evaluate the incidence of clinical lymphedema following adjuvant proton-based radiotherapy (RT) in breast cancer (BC) patients. Materials and methods: We performed a retrospective review of our institutional database to identify BC patients treated with adjuvant proton-based RT. Patients receiving re-irradiation for a BC recurrence or those with a history of ipsilateral chest wall radiation were excluded. Clinical lymphedema was determined by documentation in the chart at baseline and during follow-up. Results: We identified 28 patients treated with adjuvant proton-based RT who met the study criteria. Median age at diagnosis was 45 (range, 24–75). Eleven patients (39%) underwent mastectomy, and fourteen (50%) underwent axillary lymph node dissection (ALND). Median number of LNs removed was 6 (range, 1–28). Nineteen patients (68%) received neoadjuvant chemotherapy. Median whole breast/chest wall dose delivered was 50 Gy (range, 44–54.0 Gy). Target volumes included the axillary and supraclavicular lymph nodes in all patients and internal mammary lymph nodes in 27 (96%) patients. Mean dose to the axilla was 49.7 Gy, and mean dose to 95% of the axillary volume (D95) was 46.3 Gy (94% of prescription dose). Mean dose to supraclavicular (SCV) volume was 47.7 Gy, and D95 was 44.1 Gy (91% of prescription dose). Grade 3 dermatitis occurred in 14% of patients. Five patients (18%) had clinical lymphedema, 4 from the ALND subset (n = 14). Conclusions: The incidence of clinical lymphedema after proton-based RT is comparable to rates reported with photon-based RT with comprehensive nodal coverage

Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer.

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 × 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 × 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 × 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 × 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction

Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer

In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction

Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer

Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10-8) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P &lt; 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10-4 and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10-9) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10-69). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction