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PubMed2026

[A Case of Stage Ⅳ Lung Adenocarcinoma with Bilateral Breast Metastases Mimicking Inflammatory Breast Cancer].

Breast metastases from primary lung cancers with inflammatory breast cancer (IBC)-like features are rare. Here, we report a patient with bilateral breast metastases from an advanced lung adenocarcinoma that mimicked IBC. A 67-year-old woman was diagnosed with right middle lobe lung adenocarcinoma with pleural and peritoneal dissemination (cT2aN2M1c, cStage ⅣB) and received systemic therapy. Twenty-nine months later, skin erythema and edema appeared in both breasts, suggesting bilateral IBC. Core needle biopsies of both breasts revealed atypical carcinomas without intraductal or lobular in situ components. Immunohistochemistry showed thyroid transcription factor-1 and Napsin A positivity and GATA3 negativity, supporting the diagnosis of metastatic lung adenocarcinoma of the breasts. Comprehensive genomic profiling of the breast specimen revealed an EGFR exon 19 deletion, and osimertinib achieved disease control within 1 year. This report highlights a diagnostic pitfall in which lung adenocarcinoma metastasis to the breast mimics IBC and underscores the importance of biopsy, an appropriate immunohistochemical panel, and molecular testing to establish a correct diagnosis and guide optimal systemic therapy.

Humans↗
PubMed1981

Benign breast disease: estriol proportions and family history of breast cancer.

Urine samples were analyzed for estrone (E1), estradiol (E2), and Estriol (E3) to test the hypothesis that women diagnosed with benign breast disease (high risk for breast cancer?) will have lower estriol proportions (E3/E1 + E2 + E3) than a comparison control group. Luteal urine samples were collected from 64 women recently diagnosed with benign breast disease (cases) and from 64 controls matched for age and education. Compared to their controls, benign breast disease patients had a lower mean weight (P less than 0.05), lower Quetelet's index (P less than 0.02), and higher frequency of family history of breast cancer (P less than 0.01) and of family history of any breast disease (P less than 0.01). The mean estriol proportions were similar for cases and controls before and after stratification by family history and Quetelet's index. Results of this study indicate that if women with benign breast disease are at high risk of breast cancer, that risk is not transmitted by the estriol proportion.

Adult↗
PubMedDate not supplied

Vitamin A concentration in breast adipose tissue of breast cancer patients.

Vitamin A concentration in breast adipose tissue as a risk factor for breast cancer was studied by assessing the vitamin A concentration in breast adipose tissue of women with benign breast disease (n = 45) and of those with breast cancer (n = 36). No significant differences in vitamin A concentration between the two groups were found either in premenopausal or postmenopausal subjects. The same was true with the dietary intake of vitamin A in these two groups of women. The vitamin A concentration in breast adipose tissue had a significant correlation with the dietary intake in breast cancer cases only (r = 0.42, p < 0.01). The present results support the previous suggestion that vitamin A is unlikely to be related to the risk of breast cancer.

Adipose Tissue↗
PubMed1995

Comparative allelotype of in situ and invasive human breast cancer: high frequency of microsatellite instability in lobular breast carcinomas.

To better understand the timing for presentation of allelic losses in human breast carcinogenesis, we compared the allelotypic profile of 23 in situ ductal carcinomas with that of 29 invasive ductal carcinomas. We also compared the allelotype of the invasive ductal breast carcinomas with that of 23 invasive lobular breast carcinomas. These studies were performed by means of microsatellite length polymorphisms from microdissected paraffin sections. We observed that involvement of chromosome arms 1p, 3p, 3q, 6p, 16p, 18p, 18q, 22q, and possibly 6q and 11p appear to be late events in breast cancer progression because allelic losses or imbalances affecting these areas were observed with very low frequency at the in situ stage. On the other hand, allelic imbalances and losses affecting chromosome arms 7p, 16q, 17p, and 17q appear to be early abnormalities because they were observed in approximately 25-30% of ductal carcinoma in situ lesions. Allelic losses and imbalances affecting the 8p arm were frequently observed in invasive lobular breast carcinomas. It was also interesting that microsatellite instability, also known as replication error (RER) phenotype, was found to occur at a high frequency in invasive lobular breast carcinomas because 9 of 23 (39%) were RER+, compared with 7 of 52 (13.5%) RER+ of breast cancers with ductal differentiation (P = 0.012, chi 2 test). Our findings provide for the first time molecular evidence suggesting that invasive lobular breast carcinomas may arise by a different mechanism of carcinogenesis than ductal carcinomas.

Adult↗
PubMed1994

Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue.

Wnt gene expression was investigated by ribonuclease protection analysis in human breast cancer, nontumorous breast tissue, and a variety of human breast cell lines. We report the expression of Wnt3, Wnt4, and Wnt7b in human breast cell lines and Wnt2, Wnt3, Wnt4, and Wnt7b in human breast tissues. Wnt3a and Wnt7a were absent in the cell lines and tissues tested. The level of expression of Wnt2 and Wnt4 was 10- to 20-fold higher in fibroadenomas than it was in normal or malignant breast tissue, and in 10% of tumors Wnt7b expression was 30-fold higher than in normal or benign breast tissues. In contrast to the mouse, in which Wnt1 and Wnt3 are involved in tumorigenesis, our results suggest that Wnt2, Wnt4, and Wnt7b may be associated with abnormal proliferation in human breast tissue.

Adult↗
PubMed1997

Mutations in BRCA1 and BRCA2 in breast cancer families: are there more breast cancer-susceptibility genes?

To estimate the proportion of breast cancer families due to BRCA1 or BRCA2, we performed mutation screening of the entire coding regions of both genes supplemented with linkage analysis of 31 families, 8 containing male breast cancers and 23 site-specific female breast cancer. A combination of protein-truncation test and SSCP or heteroduplex analyses was used for mutation screening complemented, where possible, by the analysis of expression level of BRCA1 and BRCA2 alleles. Six of the eight families with male breast cancer revealed frameshift mutations, two in BRCA1 and four in BRCA2. Although most families with female site-specific breast cancers were thought to be due to mutations in either BRCA1 or BRCA2, we identified only eight mutations in our series of 23 site-specific female breast cancer families (34%), four in BRCA1 and four in BRCA2. According to the posterior probabilities calculated for mutation-negative families, based on linkage data and mutation screening results, we would expect 8-10 site-specific female breast cancer families of our series to be due to neither BRCA1 nor BRCA2. Thus, our results suggest the existence of at least one more major breast cancer-susceptibility gene.

BRCA1 Protein↗
PubMed1997

[Silicone breast implants and breast cancer].

Sarcomas have been shown to develop next to foreign body implants, silicone included, in animal experiments. However, this carcinogenesis is not believed to have any human relevance. A review of the existing epidemiological studies suggests that women with silicone breast implants have a reduced risk for developing breast cancer. However, the presence of breast implants does obscure mammographic visualization as well as palpation of mammary tissue. This has led to the assumption that breast cancer detection could be compromised in women with breast implants. In the few studies that have dealt with this issue, women with breast implants were diagnosed with the same stage of disease as women without implants. However, the percentage of false negative mammographies was increased in one study. In conclusion, there is currently no evidence of an association between breast implants and cancer or postponed breast cancer detection.

Breast Implants↗
PubMed1997

Analysis of the FHIT gene and FRA3B region in sporadic breast cancer, preneoplastic lesions, and familial breast cancer probands.

The FHIT gene, which spans the FRA3B fragile site at chromosome 3p14.2, is a candidate tumor suppressor gene in breast and other cancers. We investigated FHIT and FRA3B for loss of heterozygosity (LOH); homozygous deletions; abnormal transcripts; and acquired/germ-line point mutations in breast cancer cell lines (n = 32), breast epithelial and stromal cell cultures (n = 18), microdissected invasive (n = 16) and ductal in situ carcinomas (n = 6), and their accompanying normal and abnormal epithelial foci (n = 14). LOH at 3p14.2, especially at FHIT intragenic marker D3S1300, was found in 6 of 16 microdissected invasive tumors and 3 of 6 ductal in situ carcinomas. In accompanying preneoplastic foci, LOH occurred in two of eight intraductal hyperplasias but not in histologically normal ductal epithelium (n = 6). Three of 32 (9%) breast cancer cell lines demonstrated homozygous deletions of FHIT exon 4 (two cases) and exon 5 (one case), which correlated with exon 4-deleted transcripts and loss of the cDNA transcript containing the coding exons 5-9, respectively. Normal mammary cultures and 31 of 32 tumor cell lines (97%) expressed wild-type coding transcripts as well as a minor exon 8-deleted message. Single-strand conformation polymorphism analysis of the coding exons in the 32 tumor and 18 normal breast cell lines and their sequencing revealed four silent polymorphisms and a germ-line histidine triad point mutation (651 G-->T) in a tumor arising in a 70-year-old woman. This mutation was also present in one of her two thus far unaffected daughters. Analysis of additional DNAs from 280 probands of high-risk breast cancer families for other FHIT exon 8 mutations detected an intronic point mutation 13 bases upstream of exon 8. Thus, we have demonstrated relatively early abnormalities of the FHIT/FRA3B region in breast cancer and discovered two rare FHIT germ-line mutations. The expression of a transcript containing the coding exons in nearly all cell lines, including those with germ-line mutations, suggests the possibility that another gene in the FRA3B region may be involved in the pathogenesis of breast cancer.

Acid Anhydride Hydrolases↗
PubMed1997

Effect of breast self-examination techniques on the risk of death from breast cancer.

OBJECTIVE: To measure the effect of breast self-examination (BSE) technique and frequency on the risk of death from breast cancer. DESIGN: Case-control study nested within the Canadian National Breast Screening Study (NBSS). SETTING: The Canadian NBSS, a multicentre randomized controlled trial of screening for breast cancer in Canadian women. SUBJECTS: The case subjects were 163 women who had died from breast cancer and 57 women with distant metastases. Ten control subjects matched by 5-year age group, screening centre, year of enrolment and random allocation group were randomly selected for each case subject. EXPOSURE MEASURES: Self-reported BSE frequency before enrolment in the NBSS, annual self-reports of BSE frequency during the program and annual objective assessments of BSE technique. OUTCOME MEASURES: Odds ratios (ORs) associated with BSE practice were estimated by conditional multiple logistic regression modelling, which permitted control of covariates. RESULTS: Relative to women who, when assessed 2 years before diagnosis, examined their breasts visually, used their finger pads for palpation and examined with their 3 middle fingers, the OR for death from breast cancer or distant metastatic disease for women who omitted 1, 2 or 3 of these components was 2.20 (95% confidence interval [CI] 1.30 to 3.71, p = 0.003). The OR for women who omitted 1 of the 3 components was 1.82 (95% CI 1.00 to 3.29, p = 0.05), for those who omitted 2 of the 3 components, 2.84 (95% CI 1.44 to 5.59, p = 0.003), and for those who omitted all 3 components, 2.95 (95% CI 1.19 to 7.30, p = 0.02). The results remained unchanged after adjustment for potential confounders. CONCLUSION: The results, obtained with the use of prospectively collected data, suggest that the performance of specific BSE components may reduce the risk of death from breast cancer.

Adult↗
PubMed1995

Mastopathy of the accessory breast in the bilateral axillary regions occurring concurrently with advanced breast cancer.

We herein report a 41-year-old Japanese woman who demonstrated advanced cancer in the left breast occurring concurrently with mastopathy of the accessory breast tissue in the bilateral axillary regions, which appeared to be metastatic lymphadenopathy. A preoperative examination, including a mammogram, US, and CT, did not provide us with a definite diagnosis of the axillary masses: it was essential to diagnose the masses preoperatively since a bilateral mastectomy with nodal dissection is called for if the right axillary masses are metastatic from a cancer in the right breast. An intraoperative cytological examination from the bilateral axillary masses revealed adenosis with fibrocystic changes in the accessory breast tissue. We therefore performed a modified radical mastectomy only on the left side. The patient was thus saved from an unnecessary mastectomy of the right breast. Based on our experience, we wish to emphasize that the accessory breast tissue should be considered for a differential diagnosis when evaluating the axillary masses in order to avoid over-surgery, especially when a patient has been diagnosed to have massive breast cancer. An intraoperative cytological examination is strongly recommended to reach a final diagnosis in such confusing cases.

Adult↗
PubMed1998

Clinical and pathological features of breast disease in Cowden's syndrome: an underrecognized syndrome with an increased risk of breast cancer.

Cowden's syndrome (CS), or multiple hamartoma syndrome, is an autosomal dominant disorder associated with benign skin tumors and an increased risk of breast cancer. In an effort to understand the basic mechanisms regulating the development of breast cancer in this patient population, as well as to define diagnostic aspects of the disorder, we describe for the first time the clinical and pathological spectrum of breast disease in CS. We obtained the clinical histories and examined the histopathology of 59 cases from 19 women with CS sent to us from a variety of institutions. The 19 women showed a spectrum of benign histopathological findings, including ductal hyperplasia, intraductal papillomatosis, adenosis, lobular atrophy, fibroadenomas, and fibrocystic change. Seventeen (89%) showed features suggestive of a breast hamartoma. Fourteen women (74%) showed malignant disease, most of which was ductal carcinoma. Twelve patients (86%) showed ductal carcinoma in situ (DCIS), and 12 (86%) showed infiltrating ductal carcinoma. One patient had only DCIS and another patient showed both infiltrating tubular carcinoma and lobular carcinoma in situ. Ten patients (71%) actually showed foci of tumor involving densely fibrotic, hamartomatous areas. In summary, we show that women with CS have a spectrum of exuberant benign and malignant breast pathology. A common benign breast lesion in CS is a densely fibrotic hyalinized nodule, whereas the most frequent breast malignancy is ductal carcinoma.

Adult↗
PubMed2002

Breast complaints and risk of breast cancer. Population-based study of 2,879 self-selected women and long-term follow-up.

The aim of this study was to provide information about risk of breast cancer (BC) in women with breast complaints undergoing spontaneously clinical examination. The records of 2,879 self-selected symptomatic new patients observed consecutively were reviewed, and the chief breast complaint such as pain, lump and nipple discharge had been recorded. Patients were divided in three groups: Group A, 1,186 (41.2%) patients aged < 41 years; Group B, 809 (28.1%) patients aged 41-55 years; and Group C, 884 (30.7%) patients aged > 55 years. Pain was most common (P < 0.01) in Group A (60.8%), and lump in Groups B (53.3%) and C (89.7%). A total of 318 (11.0%) women had histologically confirmed BC (Group A = 3.5%, Group B = 30.5%, Group C = 66.0%), accounting for 3.2, 16.4 and 12.0% of patients with pain, lump and nipple discharge, respectively. Breast complaints were equally (P= NS) distributed between patients with and without BC. The relative risk (RR) of BC developing ranged between 0.5-1.4, 0.5-1.9, and 0.6-3.0 in Groups A, B, and C, respectively. It ranged between 0.3 and 0.7 in patients with breast pain, and was significantly higher (RR = 1.9-3.0) only in patients with breast lump aged > 40 years. In conclusion, in symptomatic patients BC risk is strictly related to age, and independent of the referred symptoms. Therefore, further investigations have to be warranted only when risk factors different from breast complaints are present.

Adult↗
PubMed1998

Cyclin D1 gene amplification and protein expression in benign breast disease and breast carcinoma.

Cyclin D1 plays a critical role in regulating cell-cycle progression. Gene amplification and protein overexpression of cyclin D1 have been detected in breast cancer but little is known concerning whether these changes occur in normal breast tissue and in breast lesions associated with increased risk of development of invasive breast cancer. We looked for cyclin D1 gene amplification and protein overexpression in 30 cases of benign breast disease (16 epithelial hyperplasias without atypia and 14 atypical ductal hyperplasias) and 18 ductal carcinomas in situ by use of differential PCR and immunohistochemical staining. We compared the resulting frequencies to those in 15 cases of normal breast tissue and 17 invasive ductal carcinomas. We found cyclin D1 gene amplification in 15% of those with normal breast tissue, 19% of those with epithelial hyperplasia without atypia, 27% of those with atypical ductal hyperplasia, 35% of those with ductal carcinoma in situ, and 25% of those with invasive ductal carcinoma; corresponding figures for protein overexpression were 13, 13, 57, 50, and 64%. These results suggest that cyclin D1 amplification and protein overexpression can occur before histologic alterations are seen but that the frequencies of these changes are higher in histologic lesions with cellular atypia (atypical hyperplasia and ductal carcinoma in situ), reaching frequencies similar to those observed in invasive carcinoma.

Breast↗
PubMed2005

Breast conserving surgery and accelerated partial breast irradiation using the MammoSite system: initial clinical experience.

HYPOTHESIS: Balloon catheter-based accelerated partial breast irradiation (APBI) may result in desirable short-term outcomes in patients undergoing breast conserving surgery. DESIGN: Prospective consecutive case series. SETTING: Tertiary multidisciplinary referral center. PATIENTS: Forty selected patients with invasive breast carcinoma undergoing breast conserving surgery and MammoSite device placement. INTERVENTIONS: Breast conserving surgery, sentinel and/or axillary node dissection, placement of the new balloon catheter applicator (MammoSite device), and APBI. MAIN OUTCOME MEASURES: Infection, early and late seroma, device explantation, time to initiating APBI, acute toxic effects on the skin, and cosmesis using the Harvard Scale. RESULTS: Thirty-nine patients underwent MammoSite device placement at the time of lumpectomy; 1 patient underwent percutaneous device placement after lumpectomy. Nineteen patients (49%) had drainage catheters placed in the breast cavity at the time of lumpectomy. Wound infection developed in 3 patients (8%). Five devices (12%) were explanted because of unfavorable final pathological findings or infection. The mean time to the start of APBI in patients who did not undergo simultaneous drain placement was 7.2 days (range, 5-12 days), compared with 5.1 days (range, 3-8 days) in patients who did (P = .008). With a mean follow-up of 13.3 months (range, 2-28 months), patients completing APBI had limited toxic effects on the skin, with excellent or good cosmetic results in 39 patients (97%). CONCLUSIONS: Use of the MammoSite system in APBI has favorable short-term outcomes. Infection and radiation treatment delay are common and may warrant use of perioperative antibiotics and drain placement, respectively. A small number of patients who have device placement at the time of lumpectomy will require explantation because of unfavorable final pathological findings. Short-term outcomes of MammoSite brachytherapy support further studies comparing APBI with standard whole breast irradiation in patients undergoing breast conserving surgery.

Adult↗
PubMed1996

Alpha-tocopherol and hydroperoxide content in breast adipose tissue from patients with breast tumors.

The study of the relationship between dietary intake of vitamin E and the risk of breast cancer has not yielded definite conclusions with respect to causality, possibly due to methodological issues inherent to nutritional epidemiology. To avoid the pitfalls of dietary recalls, alpha-tocopherol content of adipose tissue was used as a biochemical indicator of long-term dietary intake of vitamin E. alpha-tocopherol and hydroperoxides were measured in breast adipose tissue obtained at the time of diagnosis from 70 patients with early breast cancer. Thirty women with non-malignant breast tumors served as control. Lipid peroxidation was monitored by quantifying conjugated dienes spectrophotometrically and by assaying hydroperoxides with an iodometric method; alpha-tocopherol was measured by HPLC associated with fluorescence detection. Mean alpha-tocopherol value in breast adipose tissue was significantly lower in breast cancer patients than in control patients, whereas the hydroperoxide content was significantly higher in cancer patients than in controls. The alpha-tocopherol concentration in adipose tissue was not correlated with the clinical status of the patients with respect to age, menopausal status or body mass index. We conclude from this pilot study that breast cancer is associated with a low content of alpha-tocopherol in breast adipose tissue, and with an altered lipid oxidation pattern, which might be related to a low antioxidant status.

Adipose Tissue↗
PubMed1996

Cyclin gene amplification and overexpression in breast and ovarian cancers: evidence for the selection of cyclin D1 in breast and cyclin E in ovarian tumors.

Evidence of the involvement of cyclin genes in genetic alterations in human cancer is growing. In the present study, we investigated the amplification, in human breast and ovarian cancer, of 5 cyclin genes; cyclin A, cyclin D1, cyclin D2, cyclin D3 and cyclin E. For this purpose, a series of 1,171 breast and 237 ovarian tumors tested for DNA amplification by Southern blotting and a subset of 132 breast and 22 ovarian cancers were analyzed for RNA expression levels by slot-blot and Northern blotting. In breast tumors, only cyclin D1 was found to be activated in a sizeable fraction of the tumors (amplification 12.6%, overexpression 19%). Cyclin A, D2, D3, and E genes never, or only on rare occasions, showed increased DNA copy numbers and were never found overexpressed at the RNA level. Amplification of cyclin D1 correlated with ER+ breast cancer and the presence of lymph-node metastasis. Interestingly, we were also able to determine an association with invasive lobular carcinoma. Our data suggest that cyclin D1 activation determines the evolution of a particular subset of estrogen-responsive tumors. Data obtained in ovarian tumors contrasted with observations in breast cancer. Cyclin D1 DNA amplification was much less frequent in ovarian than in breast tumors (3.3% vs. 12.6%), whereas cyclin E amplification and overexpression were observed in a significant number of cases (12.5% and 18.0% respectively). Cyclin A, cyclin D2 and D3 rarely showed anomalies at the DNA level and were never overexpressed. No clear correlation could be observed between amplification of the cyclin E gene and tumor type, stage or grade in ovarian cancer. Data presented here suggest distinct pathways of cyclin activation in human breast and ovarian cancer.

Blotting, Northern↗
PubMed2003

Disruption of the expected positive correlation between breast tumor size and lymph node status in BRCA1-related breast carcinoma.

BACKGROUND: A positive correlation between breast tumor size and the number of axillary lymph nodes containing tumor is well established. It has been reported that patients with BRCA1-related breast carcinoma are more likely than patients with nonhereditary breast carcinoma to have negative lymph node status. Therefore, the authors questioned whether the known positive correlation between tumor size and lymph node status also was present in women with BRCA1-related breast carcinomas. METHODS: The relation between the greatest dimension of the resected breast tumor (size) and the presence of positive axillary lymph nodes (expressed as a percentage of all lymph nodes examined) was evaluated in 1555 women with invasive breast carcinoma who were ascertained at 10 centers in North America between 1975 and 1997. There were 276 BRCA1 mutation carriers, 136 BRCA2 carriers, and 1143 women without a known mutation (208 BRCA1/BRCA2 noncarriers and 935 untested women). Patients were stratified according to tumor size, and odds ratios were estimated for the presence of positive lymph nodes with increasing tumor size. RESULTS: A highly significant positive correlation between tumor size and the frequency of positive axillary lymph nodes was seen for BRCA1/BRCA2 noncarriers, for BRCA2 carriers, and for untested women (overall P < 0.0001 for each). In contrast, there was no clear correlation between tumor size and positive lymph node status in BRCA1 carriers (overall P = 0.20). CONCLUSIONS: The relation between tumor size and lymph node status in patients with breast carcinoma appears to be different in BRCA1 carriers compared with BRCA2 carriers and noncarriers. These findings have important implications for estimating the route of metastatic spread and for evaluating the effectiveness of early diagnosis in patients with BRCA1-related breast carcinoma.

Breast Neoplasms↗
PubMed2005

Appropriateness of breast-conserving treatment of breast carcinoma in women with germline mutations in BRCA1 or BRCA2: a clinic-based series.

BACKGROUND: Although BRCA1 and BRCA2 were identified in 1994 and 1995, respectively, to the authors' knowledge the optimal management of women with BRCA-associated breast carcinoma remains incompletely defined. The current study evaluates the appropriateness of breast-conserving therapy (BCT) in women with BRCA mutations. METHODS: Between May 1992 and October 2003, 87 female participants in genetic testing protocols were identified who 1) were found to have deleterious germline BRCA mutations and 2) reported a history of invasive breast carcinoma that was treated with wide local excision and radiation therapy. Clinical records were reviewed and follow-up was updated. RESULTS: The 87 subjects underwent BCT for 95 invasive breast tumors (8 women received BCT for metachronous bilateral tumors). In all 95 treated breasts, the 5-year and 10-year probabilities of metachronous ipsilateral breast carcinoma (MIBC) were 11.2% and 13.6%, respectively. Among the 87 subjects, the 5-year and 10-year probabilities of metachronous contralateral breast carcinoma (CBC) after treatment of the index tumor were 11.9% and 37.6%. No clinical factors were identified that were associated with either MIBC or CBC, including the use of tamoxifen or chemotherapy. CONCLUSIONS: Women with BRCA-associated breast carcinoma who undergo BCT appear to have risks of MIBC that are similar to those reported for young women without known mutations. The indications for unilateral mastectomy in this group of women should be the same as those for women with nonhereditary carcinoma. However, significant risks of CBC and possibly late MIBC may prompt the serious consideration of bilateral mastectomy as a preventive measure.

Adult↗