Breast cancer during pregnancy of Luminal A type overexpressed CXCL13.

Pregnancy-associated breast cancer has been increasing. In this study, we analyzed patients with breast cancer that occurred during pregnancy (PrBC) and compared their genetic profiles with those of patients with breast cancer that did not occur during pregnancy, within 1 year after childbirth nor during lactation (non-PrBC). We performed gene expression analyses of patients with PrBC and non-PrBC using microarrays and qRT-PCR. Microarray analysis showed that 355 genes were upregulated in the luminal-type PrBC group compared to those in the non-PrBC group. The C-X-C motif chemokine ligand 13 (CXCL13) gene was the most upregulated in the PrBC group compared to that in the non-PrBC group, especially in the luminal A-type (p = 0.016). This result was corroborated by the qRT-PCR analysis of microdissected cancer cells (p < 0.001). A negative correlation was observed between CXCL13 and estrogen receptor 1 (ESR1) mRNA expression levels in luminal A-type breast carcinoma (p < 0.001). Our results provide clues for a better understanding of breast cancer pathogenesis during pregnancy.

Prognostic effect of subsequent childbirth after the diagnosis of breast cancer using propensity score matching analysis.

BACKGROUND: Among younger patients, one of the important concerns is whether they can give birth safely. Although previous studies have investigated this topic, many aspects remain unclear owing to potential biases. We aimed to evaluate the prognostic effect of subsequent childbirth after the diagnosis using propensity score matching. METHODS: A single-center retrospective cohort study was conducted. This study included patients aged ≤ 45 years, diagnosed with breast cancer between 2005 and 2014. Patients with and without subsequent childbirth were assigned to the childbirth and non-childbirth cohorts, respectively. Relapse-free survival (RFS) and overall survival (OS) of the childbirth cohort were compared with those of the non-childbirth cohort. The covariates in the propensity score model included age, tumor size, node status, number of preceding childbirths before the diagnosis, estrogen receptor, and human epidermal growth factor receptor 2 status. RESULTS: 104 patients with childbirth and 2250 without childbirth were assigned to the respective cohorts. At a median follow-up of 82 months, the childbirth cohort showed a significantly longer RFS than the non-childbirth cohort (HR = 0.469 [0.221-0.992]; p = 0.047). There was no significant difference in the OS (HR = 0.208 [0.029-1.494]; p = 0.119). After matching, subsequent childbirth was not significantly associated with RFS (HR = 0.436 [0.163-1.164], p = 0.098) and OS (HR = 0.372 [0.033-4.134], p = 0.402). CONCLUSIONS: Subsequent childbirth was not associated with an increased risk of relapse and mortality. It is important to make younger patients aware of these novel findings and aid them in their decision-making.

Impact of childbirth history on dense breast in mammographic screening: a cross-sectional study.

BACKGROUND: The evaluation of breast density is important, because dense breast has been shown to be associated with increased risk of breast cancer and a greater risk of a false-negative diagnostic performance due to masking a tumor. Although the relationship between parity and dense breast is under investigation, conclusive evidence is lacking. We aimed to investigate whether parity affects breast density. METHODS: The study design is a cross-sectional study. The subjects are healthy Japanese women who underwent opportunistic mammographic screening at the center for preventive medicine at a single institution from January 2016 to December 2018. Clinical characteristics and lifestyle factors were obtained from questionnaires. Breast density was categorized into 4 groups, namely, almost entirely fatty dense, scattered fibroglandular dense, heterogeneously dense, and extremely dense, according to the Breast Imaging Reporting and Data System. Heterogeneously and extremely dense were considered collectively as dense breast. Multivariate logistic regression analysis was conducted to investigate the relationship between parity and dense breast among premenopausal and postmenopausal women separately. RESULTS: 7612 premenopausal and 9252 postmenopausal women were investigated. Dense breast was shown in 62.6% of nulliparity, 57.3% of single parity, 47.3% of two parity, 37.6% of more than two parity among premenopausal women, and in 41.6% of nulliparity, 31.1% of single parity, 19.3% of two parity, 10.1% of more than two parity among postmenopausal women. For premenopausal women, two parity, single parity and nulliparity showed a higher risk for dense breast with statistically significance (Odds Ratio (OR) adjusted for potential confounding factors: 1.458 (95% Confidence interval (CI); 1.123-1.894), 2.349 (95%CI; 1.801-3.064), 3.222 (95%CI; 2.500-4.151), respectively), compared with more than two parity. For postmenopausal women, two parity, single parity and nulliparity had a higher risk (OR: 1.849 (95%CI; 1.479-2.312), 3.023 (95%CI; 2.385-3.830), 4.954 (95%CI; 3.975-6.174), respectively) with statistically significance, compared with more than two parity. CONCLUSIONS: Parity showed an inverse trend of having dense breast among both premenopausal and postmenopausal women. In particular, nulliparous women need to recognize their higher risk of dense breast. In the future, the declining fertility rate may affect the prevalence of dense breast in the world.

Anterior Neck-scar Contracture Reconstruction Using a Long Skin-pedicled Flap.

We previously reported cases of anterior-neck reconstruction using super-thin and perforator-supercharged skin-pedicled flaps harvested from the pectoral area and back. Here, we reconstructed a neck-scar contracture with a long skin-pedicled flap from the pectoral area that survived without congestion despite not being supercharged with a perforator, as planned. The patient, a 67-year-old man, was admitted to our hospital due to neck-scar contracture after a chemical burn 3 years previously. During surgery, the scar was resected above the platysma. A large, 19 × 6-cm skin-pedicled flap was elevated from the left pectoral area. We planned to supercharge the flap by anastomosing the second intercostal perforator to the flap periphery but could not confirm the perforator intraoperatively. To promote flap survival, we did not elevate the flap pedicle more than absolutely necessary and then manipulated the flap very carefully. The flap survived fully and the contracture was effectively released. Thin flaps are useful for reconstructing exposed areas such as the face, neck, and dorsum of the hands that require good outcomes in terms of both function and aesthetics. However, if the flap is too large, ischemia/congestion could arise in the periphery unless the blood flow is stabilized by attaching a perforator. In our case, supercharging was not possible and we had to resort to careful intraoperative maneuvers to ensure flap survival. This approach was successful and suggests that although supercharging of thin and large flaps is preferred, unexpectedly unsuperchargeable flaps can be rescued by careful and finely tuned surgical judgment and techniques.

Accuracy of morphologic change measurements by ultrasound in predicting pathological response to neoadjuvant chemotherapy in triple-negative and HER2-positive breast cancer.

BACKGROUND: Neoadjuvant chemotherapy (NAC) is standard therapy in triple-negative breast cancer (TNBC) and HER2-positive breast cancer (HER2 + ve BC). There are concerns about the accurate imaging modalities to measure residual tumor during or after NAC. Up to now no standard imaging method for monitoring the efficacy of NAC has been established, and few reports showed ultrasonographic change. We aimed to assess the echogenicity in ultrasonography (US) as the predictive marker of pathological complete response (pCR) for not only TNBC, but also HER2 + ve BC. Furthermore, we also investigated the change in depth (D) and width (W) of the tumor as the predictive value of pCR. METHODS: We retrospectively reviewed a consecutive 59 patients with TNBC and 41 patients with HER2 + ve BC who received NAC. In all of 100 patients, echogenicity, D and W of the tumor were measured before (pre-NAC) and after NAC (post-NAC). The tumor echogenicity was measured at representative region of interest (ROI), and calculated as the relative comparative assessment with fat echogenicity (ROI ratio). RESULTS: pCR was significantly associated with higher post-NAC ROI ratio in TNBC (p = 0.010), while there was no association in HER2 + ve BC (p = 0.885). pCR was significantly associated with smaller sizes of post-NAC D and W in TNBC (p = 0.001, 0.003), while no trend was observed in HER2 + ve BC (p = 0.259, 0.435). The area under the curve (AUC) for post-NAC ROI ratio and D were 0.701, 0.755, respectively. Combined with them, AUC became higher up to 0.762. CONCLUSION: TNBC and HER2 + ve BC showed different morphologic features of residual disease. Echogenicity and tumor size after NAC were both useful to predict pCR for TNBC, but not HER2 + ve BC. In future, radiological imaging needs to be analyzed in terms of breast cancer subtypes.

Breast reconstruction after risk-reducing mastectomy in BRCA mutation carriers.

BACKGROUND: Breast reconstruction is a favorable option for women with BRCA1 or BRCA2 mutations (BRCA1/2Mut+) who undergo risk-reducing mastectomy (RRM). We assessed characteristics of patients who underwent RRM, with or without breast reconstruction. METHODS: We included 46 patients with BRCA1/2Mut+ who underwent RRM from July 2011 to December 2017. RESULTS: Among the 46 patients who underwent RRM, 3 had not been diagnosed with breast cancer (BC) and 43 had cancer in a single breast; 33 patients (71.7%) underwent breast reconstruction with RRM; and 13 patients (28.3%) did not undergo breast reconstruction. All of 3 patients who had not been diagnosed with BC underwent bilateral RRM with breast reconstruction. There was no significant difference of clinical characteristic between patients undergoing RRM with and without breast reconstruction. However, patients who decided to undergo RRM with the current diagnosis of BC had significantly higher rates of RRM with breast reconstruction than that of patients with a past history of BC (P = 0.043). The rate of nipple-sparing mastectomy (NSM) in patients with breast reconstruction was significantly higher (28 of the 37 breasts, 75.7%) than that in patients without reconstruction (3 of the 14 breasts, 21.4%) (P < 0.001). Two patients who had complications underwent RRM with breast reconstruction, and one of them had a history of irradiation after lumpectomy. CONCLUSIONS: For BRCA1/2Mut+ patients, the decision of taking RRM with the diagnosis of current BC might affect whether they undergo immediate breast reconstruction with RRM. These patients who undergo RRM with breast reconstruction preferred NSM to skin-sparing mastectomies.

Predictive and prognostic value of stromal tumour-infiltrating lymphocytes before and after neoadjuvant therapy in triple negative and HER2-positive breast cancer.

AIM: Lymphocyte predominant breast cancer (BC) is associated with higher pathological complete response (pCR) rate after neoadjuvant therapy (NAT) and favorable outcome in triple negative breast cancer (TNBC) and HER2+ BC. The predictive and prognostic impact of stromal tumour-infiltrating lymphocytes (TILs) after NAT and the change of TILs before (pre-) and after (post-) NAT are not well studied. We aimed to assess the predictive and prognostic value of pre- and post-NAT TILs, as well as their pharmacodynamics modulation and their change for TNBC and HER2+ BC. MATERIALS AND METHODS: Two-hundred and nine consecutive patients (n = 80 TNBC, n = 129 HER2+ BC) who received NAT between 2001 and 2009 in a single institution were included. We evaluated the association between pre-NAT TILs and pCR, and the association between pre- and post-NAT TILs, as well as their immunodynamics change with relapse-free survival (RFS) for patients with residual disease (RD). RESULTS: Low pre-NAT TILs compared to int/high were significantly associated with lower pCR rate (TNBC: 4.0% vs 43.6%; HER2+ BC: 26.0% vs 51.9%). The median follow-up period was 98 months. In TNBC with RD, low pre-NAT TILs showed significant association with shorter RFS (HR = 3.844 [1.190-12.421], p = 0.024) in multivariate analysis. Low post-NAT TILs showed borderline significant association with shorter RFS (HR = 2.836 [0.951-8.457], p = 0.061). The change in TILs was not associated with RFS. In HER2+ BC, low pre-NAT TILs were not associated with RFS. CONCLUSION: In TN and HER2+ BCs, low pre-NAT TILs tumours had a low likelihood of achieving pCR. In TNBC with RD, both low pre- and post-NAT TILs were associated with shorter RFS. These results suggest that TILs information should be taken into account when additional therapies may be given in the post-neoadjuvant setting.

Magnetic Resonance Imaging Combined With Second-look Ultrasonography in Predicting Pathologic Complete Response After Neoadjuvant Chemotherapy in Primary Breast Cancer Patients.

BACKGROUND: Magnetic resonance imaging (MRI) or ultrasonography (US) alone is limited in the ability to predict the pathologic complete response (pCR) accurately after neoadjuvant chemotherapy (NAC). The aim of the present study was to predict the pCR using MRI combined with second-look US in primary breast cancer patients. MATERIALS AND METHODS: A total of 1274 consecutive primary breast cancer patients who were examined by MRI and second-look US before and after NAC and had undergone breast-conserving surgery from 2004 to 2014 were included. The positive predictive value (PPV) of a clinical complete response (cCR) by MRI alone and MRI plus US was assessed. A CR was defined as no residual invasive carcinoma. The presence of a residual in situ component was also assessed (ypTis). RESULTS: Of the 1274 patients, 333 (26.1%) had a pCR (ypT0/is), and 102 (8.0%) had a residual in situ component (ypTis). A cCR was found in 247 patients (19.4%) using MRI alone and in 182 patients (14.3%) using MRI plus US. The PPV for a cCR using MRI alone was 79.4% and the PPV for MRI plus US was 86.8%. The PPV for a cCR by MRI plus US was the greatest at 98.1% in the estrogen receptor-negative (ER-)/human epidermal growth factor receptor-positive (HER2+) group (86.5% in the ER+/HER2+, 83.0% in the ER-/HER2-, and 64.7% in the ER+/HER2- groups). The PPV for residual in situ component was as low as 72.2%. CONCLUSION: Our results have shown that MRI combined with second-look US in predicting for a pCR was useful compared with MRI alone, especially for ER-/HER2+. However, it was difficult to predict for the presence of a residual in situ component. Our ongoing prospective multi-institutional study has shown that adding vacuum-assisted biopsy to MRI plus second-look US is warranted to improve the prediction of pCR for omitting breast surgery.

[The Role of Preoperative Chemotherapy Depending on Breast Cancer Subtype].

Following the discovery that the prognostic impact of preoperative chemotherapy depends on the primary breast cancer subtype, the treatment strategy for primary breast cancer changed. Pathologic complete response(pCR)with preoperative chemotherapy is predictive of a favorable prognosis in patients with HER2 type or triple-negative type breast cancer, but not in patients with ER-positive/HER2-negative, the so-called Luminal type, breast cancer. However, the role of preoperative chemotherapy in patients with Luminal-B type breast cancer who may need chemotherapy should be further assessed. Recent studies have reported severalsubtypes of triple-negative breast cancer, distinguishable by gene expression analysis, which may respond differently to treatment. Furthermore, novel agents, including pertuzumab or T-DM1 for HER2 type breast cancer, bevacizumab or PARP inhibitors for triple negative-breast cancer, or combination regimens with these novelagents, are expected to achieve higher pCR rates and improve patient prognosis. The tumor microenvironment may also play an important role in predicting treatment response or prognosis. It is important that tailor-made treatment strategies for patients with primary breast cancer, especially for patients who will not respond favorably to current standard therapies, consider both the treatment effects and the medicaleconomic effects.

Successful surgical management for duodenum obstruction in a 66 year-old woman previously undiagnosed intestinal malrotation.

Intestinal malrotation is a congenital abnormality and is rarely seen in the adulthood. Most adult cases would be classified to the non-rotation type with Ladd's band and Ladd procedure is the treatment of choice. A 66 year-old woman admitted to our hospital due to duodenum obstruction. Several tests revealed that she had intestinal malrotation previously undiagnosed. Operative findings showed the fusion of duodenum with jejunum by the incomplete Treitz ligament. There was no Ladd's band and the right colon was unfixed. Dissection of the fusion completely released her symptom and she discharged without any complication. This is the first report of untypically intestinal malrotation in the adulthood without Ladd's band.