[A Case Report of Adenomyoepithelioma Coexisting with Apocrine Carcinoma in Contralateral Breasts].

Adenomyoepithelioma(AME)of the breast is a rare condition, and comorbidity with carcinoma is even more unusual. Herein, we report a case of both AME and apocrine carcinoma in different breasts of a single patient. A 48-year-old woman presented to our clinic with a right breast tumor. Fine needle aspiration cytology(FNAC)was indeterminate and suspicious for both papilloma and non-invasive ductal carcinoma, but excisional biopsy indicated an AME. Immuno-histochemical staining showed EMA(+), AE1/3(+), and CK7(+)mammary duct cells and αSMA(+), CK5/6(+), and p63(+) myoepithelial cells. Six months later, the patient noticed a left breast tumor, and although FNAC indicated no malignancy, after 6 additional months, the tumor size had increased and a mammography revealed tumor microcalcification, suggesting malignancy. Vacuum-assisted biopsy revealed an apocrine carcinoma. The patient underwent partial mastectomy and sentinel node biopsy, followed by radiotherapy and chemotherapy. The post-surgical pathology was pT1pN0M0, Stage Ⅰ, triple- negative, and the patient was disease-free for 12 years postoperatively. To our knowledge, this is only the second case of AME and breast cancer in different breasts reported in Japan.

[Five Cases of Breast Cancer Developed after Silicone Breast Implant].

We report 5 cases of breast cancer that developed after cosmetic augmentation using silicone breast implants. The chief complaints were breast tumor in 3 cases, skin change in 1 case, and nipple bleeding in 1 case. Intervals between silicone breast implants and breast cancer surgeries ranged from 10 to 31 years. The pTNM stages included were Stage 0, Ⅰ, ⅡA, ⅢB, and Ⅳ, respectively, and the subtypes included were 3 Luminal types and 2 Luminal-HER2 types. Silicone bag rupture was noted in 1 case, and all bags were removed during surgery. The breast cancer surgeries performed were four breast- conserving surgeries and one mastectomy. The follow-up period ranged between 1.8 and 14 years(mean 5.1 years). All cases survived, but 2 cases had recurrences; the Stage ⅢB case experienced lung metastasis 2 years postoperatively and Stage Ⅳ case had induced pCR by chemotherapy postoperatively, but therapeutic self-interruption led to recurrences at the contralateral axillary nodes and contralateral breast and lung metastases 3 years postoperatively. Judging from limited reports of breast cancer after silicone breast implant in Japan, their incidence seems to be extremely low, and the incidence in our clinic during these 15 years(5 out of 1,851 primary breast cancers)is 0.27%.

[Nine Cases of Pregnancy and Delivery after Breast Cancer].

The present study reviewed 9 cases of pregnancy and delivery after breast cancer in our clinic, between 2007 and 2019, to evaluate treatment options for their safe and successful management. The mean age at primary surgery was 31.7 years(27- 37); the study included 1, 5, 2, and 1 cases of pTNM Stage 0, Ⅰ, ⅡA, and ⅡB, respectively. The pregnancies were allowed after at least 1 year since completion of treatment to wash out chemotherapy or endocrine therapy agents. There were a total of 17 natural pregnancies, including 15 natural deliveries and 2 spontaneous abortions. Four patients achieved 1 birth, 4 achieved 2 births, and 1 achieved 3 births. The mean age at the first delivery after surgery was 36 years(30-40), and the highest age at the last delivery was 45 years. The molecular subtypes of breast cancer involved included 5 Luminal types, 1 Luminal-HER2 type, 1 HER2-enrich type, and 2 triple-negative types. The mean interval between the primary surgery and the first delivery was 4.3 years(3-6). Six patients were disease-free, and 3 patients experienced recurrences. Among the 3 patients with recurrence, 1 patient suffered from a local recurrence 43 months after the surgery; it was successfully resected, and she delivered 2 children after the second surgery and is now disease-free. One patient delivered 2 children after surgery; 12 years after surgery, she suffered from bone metastasis, but fortunately, endocrine therapy plus zoledronic acid treatment induced complete remission. One patient achieved pregnancy 4 years after the surgery and routine examination demonstrated the liver and bone metastases. The patient safely delivered at 9th-month pregnancy; the metastases and recurrences were treated chemo-endocrine therapy, and the patient is currently doing well. In conclusion, although the present study includes only 9 patients with 15 births, it suggests that a safe and successful pregnancy and delivery can be achieved through a variety of patient-orientated post-surgical treatment options that consider fertility preservation.

Sarcopenia as a risk factor of severe laboratory adverse events in breast cancer patients receiving perioperative epirubicin plus cyclophosphamide therapy.

PURPOSE: Sarcopenia has been reported to be associated with higher mortality and increased toxicity of chemotherapy in breast cancer patients. However, evidence from Asian countries is scarce. Here, we investigated the association between sarcopenia and the frequency of severe laboratory adverse events due to perioperative chemotherapy in Japanese breast cancer patients. METHODS: Eighty-two patients with breast cancer receiving perioperative epirubicin plus cyclophosphamide therapy were evaluated. Skeletal muscle of the cross-sectional area at the third lumbar vertebra was measured by computed tomography, and sarcopenia was defined as skeletal muscle index < 40 cm2/m2. Laboratory toxicity during all cycles of perioperative chemotherapy was assessed. The study endpoint was the frequency of severe (grade 3 or more) laboratory adverse events. RESULTS: Overall, 10 patients (12.2%) were classified as sarcopenic. The frequency of severe laboratory adverse events was 28.0%, and this was significantly higher in sarcopenic patients compared to non-sarcopenic patients (70% vs. 22.2%, odds ratio 7.9 (95% CI, 1.6-52.8), p = 0.004). Neither of body weight, body mass index, area of visceral adipose tissue, subcutaneous adipose tissue, nor skeletal muscle density was significantly associated with the frequency of severe laboratory adverse events. CONCLUSION: Sarcopenia was a significant risk factor of severe laboratory toxicity in breast cancer patients receiving perioperative epirubicin plus cyclophosphamide therapy. This finding raises the potential use of body composition assessment to predict the risk of chemotherapy toxicity and determine an individualized treatment strategy.

[Clinical Impact of First Metastasis Sites and Subtypes in the Outcome of Brain Metastases of Breast Cancer].

Brain metastasis(BM)is the final stage of metastatic breast cancer(MBC), but its course and outcomes after the first metastasis(FM)to various sites are not fully clarified. Furthermore, the survival of patients with BM appears to be improving with the recent development in MBC control according to the subtype analysis. The present study included 35 patients with BM between 2008 and 2018, and was designed to clarify the effects of the FM sites and subtypes on the outcome of these patients. Subtypes included 8 Luminal(L), 8 L-HER2+(LH), 8 HER2(H), and 11 triple-negative(TN)types, and FM sites included 14 lungs or pleurae, 4 livers, 4 brains, 4 bones, and 9 local or lymph node(LN)metastases. The median interval between FM and BM(IFB)was 33 months(M)for overall patients; 50M for LH, 37M for L, 22M for H, and 19M for TN (p=0.0463); and 24M for the high risk(HR)FM(lung, pleura, liver)and 47M for the low risk(LR)FM group(bone, local, LN)(p=0.0385). The median overall survival(OS)after BM diagnosis was 13M for overall patients; 27M for LH, 13M for H, 10M for L, and 5M for TN(p=0.0112). There were no significant differences in the OS after BM diagnosis between HR FM and LR FM patients. Multivariate analyses for OS after BM revealed that patients with HER2(+)and estrogen receptor(+) tumors had a significantly better survival(risk ratio[RR]=0.644, p=0.0413; RR=0.290, p=0.0251, respectively). Three patients are surviving longer than 10 years after BM, including 2 with L-type and 1 with LH-type tumors, and their FM sites were 1 local, 1 brain, and 1 liver. The present study indicated that subtypes and FM site(HR or LR)had significant impact on the clinical course and prognosis of patients with BM. Focusing on the subtypes and FM site can improve the early detection and treatment results of BM.

[Radiation-Associated Angiosarcoma That Developed in the Irradiated Residual Breast after Breast-Conserving Surgery for Breast Cancer-A Case Report and Review of the Literature].

We report a radiation-associated angiosarcoma(RAAS)of the breast, which is a rare but important complication after breast-conserving surgery(BCS)and radiotherapy(RT)for breast cancer. A7 2-year-old woman had undergone BCS for invasive ductal carcinoma of the right breast(pT2pN1M0, StageⅡB), followed by RT of 50 Gy; she was treated with doxifluridine and anastrozole for 5 year. She noticed a bloody cutaneous bulla in the right breast 64 months later, and the skin lesions gradually expanded. She was brought to our clinic for the treatment of massive bleeding from the skin lesions. Ulcer biopsy revealed cutaneous AS(cells were CD31[+], CD34[+], VEGF[-], and VEGF-R[+]). She underwent mastectomy and latissimus dorsal flap surgery. She died of local recurrence and liver metastasis 13 months later. RAAS is rare, but it should be considered in patients with skin lesions, such as erosion and bloody bulla, after BCS and RT for breast cancer. To our knowledge, only 12 cases of RAAS, including the present case, have been reported in Japan, and we reviewed the Japanese RAAS cases in comparison with those reported in the Western literature.

[A Case of HER2-Positive Breast Cancer with Liver Metastases Showing Three Years of Complete Response to Combination Therapy with Trastuzumabplus Pertuzumab].

A 48-year-old woman with severe interstitial pneumonitis was diagnosed with right breast cancer(invasive ductal carcinoma, T1aN1M0, ER+, PgR-, HER2 3+)and underwent modified radical mastectomy.The patient was administered tamoxifen as adjuvant therapy.However, 1 year after the mastectomy, multiple liver metastases were found and the patient received 2 anti-HER2 agents, trastuzumab and pertuzumab.A complete response(CR)was observed with the disappearance of the liver metastases in 7 months.CR was maintained for 2 years after the initiation of treatment, and then, we started trastuzumab monotherapy, which has resulted in long-term disease control.

[A Retrospective Analysis on Comparative Treatment Results for Breast Cancer between Elderly Women Aged 70 and More Than 80 Years].

This study compared the treatment results of over 80-year-old(O-80) 54 and 157 septuagenarian(70s)women with breast cancer(BC)from 1996 to 2015, to clarify the best treatment option for O-80BC patients. No differences were observed in the stages and subtypes. More than 70% of women in both groups underwent breast-conserving surgery(BCS), and 48.1% and 12.1% of O-80BC and 70sBC patients did not undergo axillary dissection, respectively. About 3.2% and 18.5% of 70sBC and O-80BC patients did not receive adjuvant therapies, respectively. Most ER-positive patients in both groups received endocrine therapy. Most patients in both groups received no intravenous chemotherapy; however, oral chemotherapy was administered in 80.3% of 70sBC and 64.8% of O-80BC patients. Approximately 75.2% of 70sBC and 11.1% of O-80BC patients received post-surgical radiotherapy(RT). No differences in both relapse-free survival and overall survival (OS)rates were observed between the 2 groups. Breast cancer-related death(57.1%)and natural death from old age (57.1%)were the most commonly observed cause of death in the 70sBC and O-80BC groups, respectively. Multivariate analyses on OS demonstrated that BCS and intravenous chemotherapy were significantly associated with poor prognosis and RT was significantly associated with better prognosis in 70sBC group, whereas BCS was significantly associated with better prognosis in O-80BC group. In conclusion, surgery, especially BCS, plays an important role in the primary treatment of O- 80BC patients; however, axillary dissection, RT, endocrine therapy, and chemotherapy cannot be performed.

[Third- and Fourth-Line Chemotherapies including Paclitaxel and Bevacizumab for Metastatic Breast Cancer].

The present study was designed to estimate the clinical efficacy of bevacizumab(BV)combined with paclitaxel(PTX)(BVPTX) as third- and fourth-line therapies in 31 patients with metastatic breast cancer(MBC). Most patients were previously treated with docetaxel and/or epirubicin. Patients were intravenously treated with BV at 5-10mg/kg and PTX at 3-5mg/kg at 2-3week intervals, and when the effect of BV-PTX was low, other chemotherapeutic agents(CTAs)and/or trastuzumab (Tr)were additionally administered. Twelve MBC patients were treated with BV-PTX alone and 19 MBC patients were treat- ed with other CTAs and/or Tr in addition to BV-PTX. No serious adverse events were observed in any regimen. Three complete responses(9.7%), 4 partial responses(12.9%), 8 stable diseases(25.8%), and 16 progressive diseases(51.6%)were observed; the response rate was 22.6%, and the clinical benefit rate was 48.4%. The median progression-free survival(PFS) and median overall survival(OS)after the initiation of BV-PTX were 7.0 and 16.0 months, respectively. All 13 HER2-positive MBC patients were treated with Tr in addition to BV-PTX, and the OS and PFS were significantly higher in the BV-PTX+Tr+ CTAs group than in the BV-PTX+Tr group. In 18 HER2-negative MBC patients, PFS and OS were better in the BV-PTX+CTAs group than in the BV-PTX alone group, though this difference was not significant. Multivariate analyses demonstrated that an additional CTAs was a variable for significantly better PFS, and additional CTAs, Tr, and endocrine therapy were significant variables for better OS. These results indicated that additional CTAs and Tr should be combined with BV-PTX for third- and fourth-line chemotherapies.

[A Multivariate Analysis of the Efficacy of Adjuvant Chemotherapy in Triple-Negative Breast Cancer].

Triple-negative breast cancers(TNBCs)are associated with early recurrence after surgery and unfavorable prognoses. To date, no effective therapies for TNBCs have been established. The present study was designed to evaluate the efficacy of adjuvant chemotherapy(ACT)for 111 TNBCs using a retrospective multivariate analysis(MVA). The intravenous(iv)ACTs included docetaxel, epirubicin, gemcitabine, and vinorelbine. The oral ACTs included UFT, doxifluridine, and cyclophosphamide. The 10-year disease-free survival(DFS)and overall survival(OS)rates were 77.5% and 86.0%, respectively. Recurrences were observed in 17 patients, and the first recurrence was most frequently located in the lung. MVA revealed that pT was a significant independent variable for poor DFS and OS. UFT was the only significant independent variable for improved DFS. The survival analysis also demonstrated that UFT alone may be an effective option for Stage I TNBCs. Furthermore, it suggested that the addition of further iv ACTs to UFT could improve the outcome in patients with Stage II-III TNBCs.

Prevalence and risk factors of bone metastasis and skeletal related events in patients with primary breast cancer in Japan.

BACKGROUND: Bone metastasis (BM) is important for studying systemic spread of breast cancer. It often causes skeletal-related events (SREs) that worsen quality of life. We investigated the prevalence and risk factors for BM and SRE using a dataset from the Breast Oncology Research Network (BORN) in Japan. PATIENTS AND METHODS: We collected data on primary breast cancer patients with node-positive or node-negative disease at intermediate to high risk of recurrence. The risk factors affecting the BM-free rate, SRE-free rate and overall survival were analyzed by using the Cox proportional hazard model. RESULTS: Data of 1,779 patients who were diagnosed with breast cancer during 2003-2005 were collected from the BORN and 1,708 cases were used for analysis. The median follow-up duration was 5.71 years. BM developed in 193 cases (11.3 %) and the BM-free rate at 5 years was 89.2 %. The annual hazard ratio of BM development differs remarkably according to the tumor subtype. SREs occurred in 133 (68.9 %) out of 193 patients and the SRE-free rate at 5 years was 92.6 %. In the multivariate analysis, clinical stage (P < 0.0001), number of lymph node (LN) metastases (P = 0.0029), tumor subtype (P = 0.034) and progesterone receptor status (P = 0.038) were independently significant risk factors for BM-free rate, but only clinical stage (P < 0.0001) and number of LN metastases (P = 0.0004) significantly correlated with SRE-free rate. CONCLUSIONS: This retrospective study clarifies the prevalence and risk factors for BM and SRE in Japanese breast cancer patients. Our results show the importance of considering subtype in the care of BM and SRE.

[Complete response in a case of advanced unresectable esophageal cancer treated by chemoradiation therapy and S-1+CDDP chemotherapy].

We report a 37-year-old woman who complained of chest discomfort as of August 2004, and was found to have advanced esophageal cancer in the upper thoracic area in December 2004.S he was diagnosed as Stage IVa (T4N1M0) because chest computed tomography (CT) indicated trachea invasion and lymph node metastasis. We diagnosed it to be a case of unresectable esophageal cancer, and she underwent chemoradiation therapy. CT showed regression of the main tumor and metastatic lymph nodes when the CRT course was completed. The main tumor disappeared macroscopically. We again considered an operation, but the CRT was so effective that the patient wished to continue CRT and underwent three courses. Endoscopy showed disappearance of the main tumor and Lugol's solution. Following this, 10 courses of the treatment with CDDP alone (CDDP 10 mg/weekly) were continued until the appearance of renal dysfunction. S-1 (100 mg/body/day)was started in September 2005. The treatment is currently ongoing, and no recurrence or metastases had occurred as of March 2009.

[A case of recurrent pancreatic cancer with lung metastasis responding to S-1 combined gemcitabine chemotherapy].

The patient was a 54-year-old male. In July 2004, he underwent resection of the pancreatic body tail region to treat pancreatic body tail cancer. On histopathological examination, the stump of the extirpated specimen was positive for tumor cells. After surgery, 10 courses of therapy with gemcitabine hydrochloride(GEM, 1, 000 mg/m(2), 3-week administration followed by 1-week discontinuation)were performed, and follow-up was continued. In February 2006, local relapse was detected. Chemotherapy with GEM was administered for 1 year and 9 months. However, in November 2007, an increase in the recurrent lesion size and right lung metastasis were noted. The regimen was switched to combination therapy with S-1 and GEM(S-1 60 mg/m(2) day, continuous administration on days 1 to 14 and 2-week discontinuation; and GEM 1, 000 mg/ m(2), administered on days 8 and 15). After the end of the 11th course, PET-CT revealed the disappearance of FDG accumulation in the recurrent and metastatic lesion sites. During the treatment period, there were no grade 3 or higher adverse reactions. The patient is being treated at the outpatient clinic (as of January 2009).

[A phase II study of weekly paclitaxel for advanced or recurrent breast cancer].

The present study investigated the efficacy and safety of weekly administration of paclitaxel (PTX) for 37 patients with advanced or recurrent breast cancer. PTX was administered at a dose of 60 mg/m(2), 6 times every 8 weeks. The mean number of treatment cycles was 2.1, and the mean number of administrations was 12.7. Response rate was 35.1%. Two patients achieved CR, 11 PR, 13 NC (3 patients of long NC), 9 PD, and 2 NE. The clinical benefit rate (CR+PR+NC) was 70.3%. Median survival time was 733 days, and median time to treatment failure was 151 days. Grade 3 or more leucopenia and neutropenia occurred in 3 of patients (8.1%), and no patients showed hypersensitivity reaction after administration of PTX. Weekly PTX (60 mg/m(2)) is one of the treatment options in advanced or recurrent breast cancer from the standpoint of palliation.

[A case of Stage IV non-operated advanced breast cancer with local recurrence thirteen years after initial therapy].

A 73-year-old woman underwent chemotherapy, radiotherapy, and hormonal therapies for right advanced breast cancer (T4, N3, M1, Stage IV) in 1993. She obtained a complete response in pathological evaluation (pCR) in 1998. For adjuvant therapies, she had been treated with hormonal therapies for five years until 2003. After the interruption of hormonal therapies, the serum levels of tumor markers had been elevated, and she had a right axillary local recurrence and a right ovarian metastasis detected by a FDG-PET/CT in February 2006. The right axillary local recurrence lesion was then resected, and she has since been treated with hormonal therapy of aromatase inhibitor (AI). The serum levels of tumor markers have been remarkably reduced, and FDG-PET/CT has showed the disappearance of the right axillary local recurrence, and the decrease of FDG accumulation of the right ovarian metastases in February 2007. We present a case of non-operated advanced breast cancer with local recurrence surviving successfully long term when treated with AI.

[A case of liver metastasis of breast cancer responding to trastuzumab plus weekly paclitaxel chemotherapy maintaining CR for 30 months].

In February, 19 9 8, a 48-year-old female patient underwent an operation for breast cancer. In November 2003, abdominal MRI revealed metastatic lesions in S 3 and S 5 of the liver, and chemotherapy (trastuzumab+weekly paclitaxel) was started, after which the metastatic lesions quickly reduced in size. No lesions could be detected by April 2004, and she was diagnosed as a complete response (CR). She now visits our hospital as an outpatient without any evidence of recurrence or any side effects of chemotherapy for 8 years and 8 months after surgery. For advanced breast cancer, there is no standard criteria regarding the time when to stop chemotherapy after obtaining a CR. This time, we experienced a case of liver metastasis of breast cancer responding to a regimen of trastuzumab plus weekly paclitaxel chemotherapy maintaining CR for a long period. We discuss the timing of the termination of chemotherapy in such a case in light of our experience and the literature.

[A case of advanced pancreatic cancer successfully treated by combined chemotherapy of S-1 and gemcitabine as second-line chemotherapy].

The patient was a 63-year-old man who suffered from advanced pancreatic cancer (T 4 N 3 M 0, Stage IVb). Palliative operation was performed for obstructive jaundice. He was treated with chemotherapy of gemcitabine (GEM) alone as first-line, and combined chemotherapy of GEM and S-1 as second-line. Both therapies were effective for this patient. Tumor marker (CA 19-9) decreased after chemotherapies (first-line: 5,692 U/mL to 70 U/mL, second-line: 4,877 U/mL to 562 U/mL). No toxic events were observed due to these therapies, so he was treated as an outpatient for about 2 years. It was considered that he had a good quality of life.

[Weekly paclitaxel therapy effective for gastric cancer with obstructive jaundice due to peritoneal dissemination--a case report].

The patient was a 61-year-old man who suffered from advanced gastric cancer, and a distal gastrectomy was performed (T3N2P1CY1, Stage IV). He was treated with chemotherapy of TS-1 alone (100 mg/day, days 1-28 with two weeks rest). Six months later he complained of lumbago and appetite loss, then was admitted to the hospital with obstructive jaundice. Total bilirubin (T-Bil) was increased to 11.3 mg/dl. CT scan examination revealed peritoneal dissemination with much ascites and dilatation of intrahepatic bile ducts. Endoscopic drainage was tried, but was discontinued due to stenosis of gastroduodenal anastomosis. Ultimately, T-Bil was elevated to 25.2 mg/dl, and he could not sleep comfortably because of a severe itch and an irritating feeling. Weekly paclitaxel therapy was started (70 mg/m(2), day 1, 8, 15, once a week for 3 weeks followed by a week rest as one cycle). One month after the first infusion therapy, the obstructive jaundice was notably improved and the ascites disappeared completely, so he was discharged. For about one year, he was treated with this chemotherapy as an outpatient. The toxic events were anemia (grade 3) and alopecia (grade 1).

Proliferative and migratory potentials of human cord blood-derived CD34- severe combined immunodeficiency repopulating cells that retain secondary reconstituting capacity.

Using the intra-bone marrow injection (IBMI) technique, we recently identified human cord blood-derived CD34- severe combined immunodeficiency (SCID)-repopulating cells (SRCs) with extensive lymphomyeloid reconstituting ability. In this study, we further investigated the hematopoietic stem cell (HSC) characteristics of these cells in terms of proliferative and migratory potentials. The absolute numbers of CD45+ and CD34+ cells generated by 1 CD34- SRC are significantly higher than those generated by 1 CD34+ SRC. It is interesting that CD34- SRCs have significantly higher migratory and proliferative abilities than CD34+ SRCs. Moreover, only 2 CD34- SRCs transplanted to primary recipients consistently showed secondary reconstituting capacity. This finding suggested the more homogenous nature of CD34- SRCs than that of the population of CD34+ SRCs. These results provided further evidence that CD34- SRCs are functionally different from CD34+ SRCs and that they are a distinct class of primitive HSCs.

A1C but not serum glycated albumin is elevated because of iron deficiency in late pregnancy in diabetic women.

OBJECTIVE We have already reported that A1C is elevated because of iron deficiency in late pregnancy among nondiabetic pregnant women. This report examined whether the same phenomenon is observed in pregnant women with diabetes. RESEARCH DESIGN AND METHODS This longitudinal study was conducted in 17 pregnant women with diabetes (20-35 weeks of pregnancy). A1C, serum glycated albumin, erythrocyte indexes, and iron metabolism indexes were measured. RESULTS A1C levels were significantly increased in late pregnancy, whereas serum glycated albumin showed no significant changes. Glycated albumin/A1C ratio, mean corpuscular hemoglobin, serum transferrin saturation, and serum ferritin were significantly decreased in late pregnancy. Serum transferrin saturation showed a significant positive correlation with glycated albumin/A1C ratio. CONCLUSIONS A1C levels, but not serum glycated albumin levels, are elevated in late pregnancy because of iron deficiency in diabetic women. Serum glycated albumin may offer an adequate marker for glycemic control during pregnancy.