Recently, aldehyde dehydrogenase (ALDH) 1 has been identified as a reliable marker for breast cancer stem cells. The aim of our study was to investigate the clinicopathological characteristics of ...breast cancers with ALDH1+ cancer stem cells. In addition, the distribution of ALDH1+ tumor cells was compared on a cell‐by‐cell basis with that of estrogen receptor (ER)+, Ki67+, or human epidermal growth factor receptor type 2 (HER2)+ tumor cells by means of double immunohistochemical staining. Immunohistochemical staining of ALDH1 was applied to 203 primary breast cancers, and the results were compared with various clinicopathological characteristics of breast cancers including tumor size, histological grade, lymph node metastases, lymphovascular invasion, ER, progesterone receptor, HER2, Ki67, and topoisomerase 2A as well as prognosis. Immunohistochemical double staining of ALDH1 and ER, Ki67, or HER2 was also carried out to investigate their distribution. Of the 203 breast cancers, 21 (10%) were found to be ALDH1+, and these cancers were significantly more likely to be ER− (P = 0.004), progesterone receptor− (P = 0.025), HER2+ (P = 0.001), Ki67+ (P < 0.001), and topoisomerase 2A+ tumors (P = 0.012). Immunohistochemical double staining studies showed that ALDH1+ tumor cells were more likely to be ER−, Ki67−, and HER2+ tumor cells. Patients with ALDH1 (score 3+) tumors showed a tendency (P = 0.056) toward a worse prognosis than did those with ALDH1− tumors. Breast cancers with ALDH1+ cancer stem cells posses biologically aggressive phenotypes that tend to have a poor prognosis, and ALDH1+ cancer stem cells are characterized by ER−, Ki67−, and HER2+. (Cancer Sci 2009; 100: 1062–1068)
Purpose: Breast cancer stem cells have been shown to be associated with resistance to chemotherapy in vitro , but their clinical significance remains to be clarified. The aim of this study was to ...investigate whether cancer stem cells
were clinically significant for resistance to chemotherapy in human breast cancers.
Experimental Design: Primary breast cancer patients ( n = 108) treated with neoadjuvant chemotherapy consisting of sequential paclitaxel and epirubicin-based chemotherapy were included
in the study. Breast cancer stem cells were identified by immunohistochemical staining of CD44/CD24 and aldehyde dehydrogenase
1 (ALDH1) in tumor tissues obtained before and after neoadjuvant chemotherapy. CD44 + /CD24 â tumor cells or ALDH1-positive tumor cells were considered stem cells.
Results: Thirty (27.8%) patients achieved pathologic complete response (pCR). ALDH1-positive tumors were significantly associated
with a low pCR rate (9.5% versus 32.2%; P = 0.037), but there was no significant association between CD44 + /CD24 â tumor cell proportions and pCR rates. Changes in the proportion of CD44 + /CD24 â or ALDH1-positive tumor cells before and after neoadjuvant chemotherapy were studied in 78 patients who did not achieve pCR.
The proportion of ALDH1-positive tumor cells increased significantly ( P < 0.001) after neoadjuvant chemotherapy, but that of CD44 + /CD24 â tumor cells did not.
Conclusions: Our findings suggest that breast cancer stem cells identified as ALDH1-positive, but not CD44 + /CD24 â , play a significant role in resistance to chemotherapy. ALDH1-positive thus seems to be a more significantly predictive marker
than CD44 + /CD24 â for the identification of breast cancer stem cells in terms of resistance to chemotherapy.
Purpose We conducted a retrospective study to assess the safety, cosmetic outcome, and patients' satisfaction after skin-sparing (SSM) and nipple-sparing mastectomy (NSM) for breast cancer with ...immediate reconstruction of the breast (SMIBR). Methods The subjects were patients, who underwent SMIBR, breast-conserving surgery (BCS), and total mastectomy (MST) between 2000 and 2004 at Osaka University Hospital. Cosmetic outcome was estimated by 4 reviewers by scoring postoperative photographs of the patients. Patient satisfaction was evaluated with a questionnaire for assessment of quality of life for Japanese breast cancer patients. Results Of the 74 patients who had undergone SMIBR, 4 developed local recurrences (5%). The local recurrence rate for SMIBR patients was greater than that for BCS (4/178) and MST (3/178, P = .10). The distant recurrence rate was similar for all three types of patients (5% for SMIBR, 5% for BCS, and 9% for MST). The median averaged score by 4 reviewers for the estimated cosmetic outcomes was 7.8 for the SMIBR and 7.5 for the BCS group ( P = .20), and for age-adjusted patients, the corresponding scores were 8.2 and 8.0 ( P = .70). There was no difference in cosmetic outcome between the SSM and NSM subgroups ( P = .09). Average scores for patient satisfaction (social activity, physical aspects, and general condition) were the same for the 3 groups. For body image, the BCS and SMIBR groups had higher scores than the MST group (p < 0.05). Average scores for questions relating to bodily pain and sexual aspects were higher for the BCS than the MST group, but were not different between SMIBR and BCS groups. Similar trends for the 3 groups were observed when patients were divided into subgroups by tumor size or axillary dissection. Conclusions SMIBR is safe with a comparatively low local recurrence rate and the same distant recurrence rate as for BCS and MST. Moreover, it results in objective cosmetic outcome and patient satisfaction as good as those for BCS, and greater patient satisfaction with body image than that for MST.
Breast-conserving therapy, where radiotherapy is performed after partial mastectomy, is a widely used surgical method that can preserve most of the breast tissue without increasing the recurrence ...rate of breast cancer. However, without reconstruction, asymmetry of the breast occurs due to the tissue defect and radiation fibrosis, producing in poor cosmetic results. In this case study, we performed staged prosthetic breast reconstruction combined with fat grafting for severe depressive deformation of the breast after breast-conserving therapy. The first surgery involved insertion of a tissue expander and fat grafting, second surgery was the reduction of injected saline volume and fat grafting, and third surgery involved exchange for an implant and fat grafting. The skin in the depressed area, which had atrophied, became soft and flexible; deformation was also improved, and the patient was satisfied with the aesthetic outcome. It is expected that fat grafting will fertilize and qualitatively improve the damaged tissue due to irradiation, reducing the complications related to the tissue expander and implant. We believe that it will be possible to correct a breast deformity after breast-conserving therapy using a tissue expander and implant, which had not been considered as a solution. The results showed that the present method can be an option for delayed reconstruction after breast-conserving therapy.
Abstract Background Areolar injection for sentinel lymph node biopsy (SLNB) in breast cancer surgery has been adopted by many institutions. However, only one study has reported the follow-up results ...for patients whose SLNB was performed with this injection method alone. Methods Three hundred eighty patients with breast cancer underwent SLNB with periareolar injection of both blue dye and radiotracer. The follow-up consisted of a physical examination every 3 months and annual mammography. Results Of 380 patients with SLNB, 261 were found to have negative sentinel lymph nodes so that no ALND was performed. At a median follow-up of 39 months (range 13–74), 2 of the 261 patients developed axillary recurrence for an axillary relapse incidence of .77%. Five-year distant disease-free survival was 96.9%, and overall survival was 99.4%. Conclusions The incidence of axillary recurrence for the areolar injection method was low and consistent with that reported in other observational studies using other injection methods.
Purpose: Several reports have demonstrated the association between high serum estrogens levels and breast cancer risk in postmenopausal
women. It is hypothesized that breast cancers arising in ...postmenopausal women with high serum estrogens levels are more likely
to be estrogen receptor (ER)-positive. Thus, we have investigated whether or not high serum estrone (E 1 ) levels are associated with ER-positive breast cancer risk in postmenopausal women.
Experimental Design: A case-control study was conducted on 71 cases (postmenopausal breast cancer patients) and 73 controls (postmenopausal healthy
women). Serum E 1 levels were examined in their association with breast cancer risk after adjustment for the various epidemiological risk factors.
In addition, clinicopathological characteristics of breast cancers arising in the women with high E 1 levels were investigated.
Results: Women in the high tertile of E 1 levels had a significantly ( P < 0.01) increased risk of breast cancer as compared with women in the low tertile odds ratio (OR), 4.14; 95% confidence
interval (CI), 1.44–11.87. Subset analysis according to the ER status showed that women in the high tertile of E 1 levels had a significantly increased risk for ER-positive breast cancer (OR, 23.79; 95% CI, 3.50–161.59) but not for ER-negative
breast cancer (OR, 1.45; 95% CI, 0.41–5.15) as compared with women in the low tertile. Tumor size and lymph node status were
not significantly different between women in the high tertile and those in the intermediate and low tertiles. But the frequency
of low-histological-grade tumors and ER-positive tumors (88 and 67%, respectively) showed a greater trend toward an increase
( P = 0.06 and P = 0.07, respectively) in women in the high tertile than those (69 and 46%, respectively) in the intermediate and low tertiles.
In addition, ER levels in ER-positive tumors were significantly ( P < 0.05) higher in women in the high tertile (245.3 ± 37.1 fmol/mg protein) than those in the intermediate and low tertiles
(134.0 ± 31.3 fmol/mg protein).
Conclusions: Postmenopausal women with high serum E 1 levels have a significantly increased risk for ER-positive, but not ER-negative, breast cancer. Breast cancers arising in
women with high E 1 levels show a high ER positivity as well as high ER content. Measurement of serum E 1 levels would be clinically useful in the selection of postmenopausal women who can benefit from prophylactic use of tamoxifen
because tamoxifen can prevent ER-positive, but not ER-negative, breast cancer.
Following unilateral breast cancer surgery, mastopexy and reduction of the unaffected breast are often performed to obtain symmetrical breasts. The use of implants in breast reconstruction results in ...a nonptotic breast. To achieve symmetry following the procedure, the unaffected side should be nonptotic too. However, no study has yet reported any indices for the design of mastopexy and reduction in this direction. We present a new method of preoperative design that uses vertical breast measurements to form nonptotic breasts according to individual breast shapes.
We performed vertical breast measurements of the unaffected breasts of 193 patients scheduled to undergo surgery for unilateral breast cancer. The vertical base dimension (VBD) and vertical surface dimension (VSD) of the ptotic and nonptotic breasts and the height of the nipple in the nonptotic breast were measured in centimeters.
The borderline between ptotic and nonptotic breasts was expressed using the formula VSD = 1.13 × VBD + 1.86. The height of the nipple in nonptotic breasts was 0.8 times the distance between the sternal notch and lowest point of the inframammary fold on the midline. From these findings, we formulated a new method for forming a nonptotic breast from a ptotic breast using an inverted T design.
These results can be used for the design of mastopexy and reduction when forming a nonptotic breast on the unaffected side. These procedures can be performed without significantly lifting the nipple–areolar complex if required during unilateral prosthetic breast reconstruction.
Usefulness of three dimensional (3D) multidetector-row CT (MDCT) images for preoperative evaluation of tumor extension was studied in primary breast cancer patients.
3D-MDCT tumor images of 143 ...tumors in 143 patients with primary breast cancer were created with the volume rendering method. The transverse tumor size (TS) and vertical tumor size (VS) were then measured in an anterior-posterior view of the 3D-MDCT images. The pathological tumor size was determined according to a map of the tumor spread prepared by pathologists using multi-sliced (3-5 mm intervals) surgical specimens and compared with the tumor size on 3D-MDCT images.
First, the optimal method for creating 3D-MDCT tumor images was determined for the first 40 patients (learning set), resulting in a fairly good correlation of tumor size on 3D-MDCT images with pathological tumor size (r = 0.983 for TS and r = 0.958 for VS). We then carried out a validation study on the next 103 patients (validation set). The 3D-MDCT tumor size's strong correlation with the pathological tumor size demonstrated a high rate of accuracy (r = 0.974 for TS and r = 0.977 for VS). Subset analyses according to histological type showed that correlation coefficients were r = 0.979 for TS and r = 0.981 for VS of invasive ductal carcinomas (n = 88), r = 0.948 for TS and r = 0.970 for VS of ductal carcinomas in situ (n = 10), and r = 0.984 for TS and r = 0.976 for VS of invasive lobular carcinomas (n = 5).
3D-MDCT images can assess breast cancer tumor extension highly accurately, and thus seems to be useful for planning the extent of resection in breast conserving surgery.
The effect of adjuvant tamoxifen treatment on bone mineral density (BMD) and bone turnover markers was studied in postmenopausal breast cancer patients. The relationship of tamoxifen's effect with ...the genetic polymorphisms of estrogen receptor (ER)-α and ER-β gene was also studied. Twenty-one postmenopausal breast cancer patients were given tamoxifen (20 mg/day) as the adjuvant treatment after the surgery. BMD of the lumbar supine (dual emission X-rays absorptiometry) and bone resorption (deoxypyridinoline, aminoterminal telopeptide of type I collagen, and carboxyterminal telopeptide of type I collagen) and formation (propeptide of type I procollagen, osteocalcin, and bone-specific alkaline phosphatas) markers were examined at baseline (before the surgery), 6 and 12 months after the start of tamoxifen treatment. Genetic polymorphisms analyzed were TA dinucleotide repeats polymorphism in the promoter region and
PvuII and
XbaI restriction fragment length polymorphism for the ER-α gene and the CA dinucleotide repeats polymorphism in the intron 5 for the ER-β gene. Tamoxifen significantly increased BMD of the lumbar spine at both 6 (
P<0.01) and 12 months (
P<0.01) after the start of tamoxifen as compared with that at baseline. The mean percent increase in BMD was 3.3% at 6 months and 2.7% at 12 months. All bone resorption and formation markers significantly decreased at both 6 and 12 months. Among the four genetic polymorphisms studied, only ER-β CA repeat polymorphism was found to be significantly associated with BMD at 12 months, i.e. BMD of the 21 CA repeats allele carriers was significantly higher than that of the non-carriers (
P=0.025). These results suggest that tamoxifen increases BMD of the lumbar supine by reducing the bone turnover in postmenopausal breast cancer patients, and this bone restoring effect of tamoxifen is more marked in ER-β 21 CA repeats allele carriers than non-carriers.
Although fat grafting is expected to become a common and widely used procedure in breast reconstruction in the future, there is little known about its effects at the follow-up after initial breast ...cancer treatment. We performed ultrasound after fat grafting and assessed the findings. On ultrasound of 126 breasts in 116 cases of breast reconstruction with fat grafting performed at our facility, tumorous lesions were found in 51 breasts and no such lesions were found in 75 breasts. In total, 151 tumorous lesions were identified. These comprised 145 cystic lesions, three mixed lesions, and three solid lesions. One of the three solid lesions was pathologically examined and was found to be benign. When fat grafting is performed for breast reconstruction, it is known to cause fat necrosis. Depending on the range of necrosis and shape, changes, such as cyst formation or scar healing, may occur and be observed on ultrasound. Although most cases are benign, a limited number of cases exhibit findings of malignancy. Therefore, the above findings need to be shared between plastic surgery and breast surgery departments.
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