COMPARATIVE ACCURACY OF MAMMOGRAPHY AND ULTRASOUND IN WOMEN WITH BREAST SYMPTOMS ACCORDING TO AGE AND BREAST DENSITY

Breast cancer is the most common cancer and the second most common cause of death from cancer in women.Th e aim of this studywas to determine which is more accurate imaging test mammography or ultrasound for diagnosis of breast cancer based on the women’s age and breast density. We examined  patients with breast symptoms, by clinical breast examination, mammography and ultrasound. A total of  breast lesions were examined by histopathology analyses. Histopathology results revealed the presence of  invasive cancers, and  benign lesions. Sensitivity varied signifi cantly with age and breast density. In the  women who had both tests, ultrasound had a higher sensitivity than mammography in women younger than  years, whereas mammography had a higher sensitivity than ultrasound in women older than  years. Th e sensitivity according to age was , for mammography and , for ultrasound. Th e specifi city according to age was ,  for ultrasound and ,  for mammography. Comparing the sensitivity of mammography and ultrasound according to the breast density indicates that mammographic sensitivity was , among women with predominantly fatty breast, but . in women with heterogeneous dense breasts, with the increase of fi bro glandular density the level of sensitivity with mammography decreases, while ultrasonographic sensitivity was , among women with predominantly fatty breast and , for heterogeneous dense breasts. Our data indicate that sensitivity and specifi city of ultrasound was statistically signifi cantly greater than mammography in patients with breast symptoms for the detection of breast cancer and benign lesions particularly in dense breast and


Introduction
Excluding cancers of the skin, breast cancer is the most common type of cancer in women today, accounting for  of every  cancers diagnosed.A woman's chance of developing invasive breast cancer at some time in her life is approximately  in  ().It is one of the leading causes of cancer mortality among women ().Breast cancer is a heterogeneous disease with no single characterized cause.Epidemiological studies have identifi ed many risk factors that increase the chance for a woman to develop breast cancer.Important risk factors for female breast cancer include early age at onset of menarche, late age at onset of menopause, a fi rst full-term pregnancy after the age of  years, a history of premenopausal breast cancer for a mother and a sister, and a personal history of breast cancer or benign proliferative breast disease.Obesity, nulliparity, and urban residence have also been associated with an increased risk of breast cancer.Mammography plays a major role in early detection of breast cancers, detecting about  of cancers at least a year before they can be felt.Th ere are  types of mammography examinations: screening and diagnostic.Screening mammography is done in asymptomatic women.Early detection of small breast cancers by screening mammography greatly improves a woman's chances for successful treatment.Screening mammography is recommended every - years for women once they reach  years of age and every year once they reach  years of age.In some instances, physicians may recommend beginning screening mammography before age  if the woman has a strong family history of breast cancer.Studies have shown that regular mammograms may decrease the risk of late-stage breast cancer in women  years of age and older (,).Diagnostic mammography is performed in symptomatic women, when a breast lump or nipple discharge is found during self-examination or an abnormality is found during screening mammography.Diagnostic mammography is more involved and time-consuming than screening mammography and is used to determine exact size and location of breast abnormalities and to image the surrounding tissue and lymph nodes.Mammography is known to a have a certain false-negative rates.According to data from the Breast Cancer Detection Demonstration Project, the false-negative rate of mammography is approximately -.Approximately - of women with a clinically suspicious abnormality, a negative mammogram, and a negative sonogram may still have breast cancer.Possible causes for missed breast cancers include dense parenchyma obscuring a lesion, poor positioning or technique, perception error, incorrect interpretation of a suspect fi nding, subtle features of malignancy, and slow growth of a lesion.().Ultrasonography has been playing an increasingly important role in the evaluation of breast cancer.Breast ultrasound is the preferable method in the case of a symptomatic patient, after clinical examination.In the case of a patient without symptoms, breast ultrasound is ascribed a higher sensitivity for detecting breast cancer in women with dense breast tissue, women under the age of  and high-risk women.Many specifi c indications for breast US have been enumerated, including:evaluation of a palpable mass incompletely evaluated at mammography;diff erentiation of a cyst from a solid nodule; evaluation of palpable lesions with associated mammographic asymmetry, no mammographic fi ndings, the presence of implants, or a history of lumpectomy or segmentectomy.Mammographically occult cancers can be detected by ultrasound in  to   of the cases depending on the patient's breast density and age (,,).Th e aim of this studywas to determine which is more accurate imaging test mammography or ultrasound for diagnosis of breast cancer based on the women's age and breast density.

Material and Methods
In Department of Radiology in University of Prishtina, between January  and September , we examined  women with breast symptoms.The mean age of the patient was  years, standard deviation (SD), ,  (age range  to  years).Breast lesions were detected by clinical breast examination, mammography and ultrasound.A total of  breast lesions were examined by histological methodology.Histopathology results revealed the presence of  invasive cancers, and  benign lesions.

Anamnesis:
To each patient, detailed history was taken including: Age at first childbearing, age at menarche, age at menopause, history of breastfeeding, number of children,history of hormone therapy, a history of premenopausal breast cancer for a mother and a sister, a personal history of breast cancer or benign proliferative breast disease, radiation, chemical exposure and smoking.

Analysis in detail:
The protocol ofdiagnosis consisted of clinical breast examination, ultrasound, mammography and histopathological examination.

Physical examination
Clinical breast examination of the whole breasts and axillary's regions was performed with the patient in the sitting position with arms both lowered and raised.In an upright position, we visually inspects the breasts, noting asymmetry, nipple discharge, obvious masses, and skin changes, such as dimpling, infl ammation, rashes, and unilateral nipple retraction or inversion.With the patient supine and one arm raised, we thoroughly palpates breast tissue, axillary's region and supraclavicular area, assessing the size, texture, and location of any masses.After the patient history is obtained and the clinical breast examination is performed, the next diagnostic step was mammography, ultrasound and biopsy.

Mammography
Conventional film-screen mammography was performed with at least two views per breast, medio-lateral oblique and cranio-caudal views.Additional views or spot compression views were obtained where appropriate.Mammograms were obtained with dedicated mammography units (Alpha RT Imaging, General Electric Medical Systems, Milwaukee).Patient younger than  years were excluded because mammography was not performed in this age group.Mammograms were interpreted according to the Breast Imaging Reporting and Data system (BI-RADS)diagnostic categories on a five-point scale, with BI-RADS  (negative),  (benign fi nding),  (probably benign),  (suspicious abnormality), and  (highly suggestive of malignancy).Breast density grades were also determined according to the BI-RADS on a scale of -, with  corresponding to a dense breast,  to a heterogeneous breast,  to scattered fi bro glandular densities and  to an almost entirely fat breast ().In this series, of  women, examinations were performed in  women (mean age: , years; SD, ,) with fatty breasts, in  women (mean age: , years; SD: ,) with scattered fi bro glandular dense breast, in  women (mean age: , years, SD: ,) with heterogeneously dense breast and in  women with dense breast (mean age: , years, SD: ,).

Breast Ultrasound
The radiologist who had performed the physical examination and who had interpreted the mammograms of that patient performed breast ultrasound.Ultrasound examinations were performed using a high-resolution unit (Aloka SSD ; Tokyo, Japanand Mindray DP Plus) with a linear array probe centred at ,  MHz.All ultrasound examinations were performed with the patient in a supine position for the medial parts of the breast and in a contra lateral posterior oblique position with arms raised for the lateral parts of the breast.The whole breasts were scanned.Diagnoses were scored on a fi ve-point scale identical to the mammographic BI-RADS categories ().

Histopathological examination
A total of  breast lesions were examined by histological methodology.Final histologic diagnosis was obtained for all patients who underwent surgical biopsy, and all cases were verifi ed by reviewing the histopathology report.Histopathology results revealed the presence of  invasive cancers and  benign lesions.

Th erapy
Treatment of patient with breast cancer was based on a multimodality approach combining surgery, radiation therapy hormonal therapy and/or chemotherapy.Treatment is tailored for an individual patient based on tumor size, axillary lymph node involvement, estrogens and progesterone status, histologic tumour type, standardized pathologic grade, and menopausal status.Lumpectomy or wide local excision was performed for patient with benign tumour.
Statistical analysis χ  test, and student t-test were used for statistical data processing.The significance of differences observed was assessed using Pearson's chi-square test, with p<, considering to be statistically significant.

Results
The study included  patients with breast symptoms, who had all undergone both mammography and ultrasound and then underwent breast surgery.A total of  breast lesions were examined by histological method, revealing the presence of  invasive cancers, and  benign lesions.The mean age of the patient was  years, ranging from  to  The sensitivity of ultrasound was significantly higher than of mammography (P<, ) (Table .).
The specificity of ultrasound was significantly higher than mammography (P<, )(Table .).
Mammography was false negative in  (, ) out of  invasive cancers;ultrasound was false negative in  out of  cancers(Table .).
Mammography was false negative in  (, ) out of  patients without cancer;ultrasound was false negative in  (, ) out of  patients without cancer (Table .).
The sensitivity of ultrasound for dense and heterogeneously dense breast was significantly higher than mammography (P<, )(Table .).
The specificity of ultrasound for dense and heterogeneously dense breast was significantly higher than mammography (P<, )(Table .).The ultrasound sensitivity of ,  was ,  greater than the mammography sensitivity of , .The sensitivity of ultrasound was significantly higher than of mammography (P<, ).Table .shows that ultrasound specifi city of ,  was , greater than the mammography sensitivity of ,.The specificity of ultrasound was significantly higher than mammography (P<,) (, , , , , , ).Table .shows that, of all cancers, , were correctly identifi ed as cancer on ultrasound but not correctly identifi ed as cancer on mammography, and , were correctly identified on mammography but not on ultrasound.Mammography was false negative in  (, ) out of  invasive cancers;ultrasound was false negative in  out of  cancers.Table .shows that, of all women who did not have breast cancer, about ,  had false-positive findings on one test but were correctly identified as not having cancer on the other test.Mammography was false negative in  (,) out of  patient without cancer, ultrasound was false-negative in  (, ) out of  patients without cancer.Table .shows that sensitivity for mammography and subsequent ultrasound for dense breast was  ( of ) and ,  ( of ), for heterogeneous dense breasts , ( of ) and , ( of ) for scattered fibro glandular dense breast ,  ( of ) and , ( of ) for entirely fatty breast , ( of ) and , ( of ).
Comparing the sensitivity of mammography and ultrasound according to the breast density, indicates that mammography is more sensitive in the dominate of fat tissue (, ) and at the scattered fi bro glandular density (, ).With the increase of fibro glandular density the level of sensitivity with mammography decreases, while with the ultrasound the level of sensitivity increase to the higher breast density ,  and heterogeneously breast density , Th e diff erences between these two diagnostic methods are signifi cant (P<,).Table .shows that comparing the specifi city of mammography and ultrasound according to the breast density,ultrasound is more sensitive in the heterogeneously dense ,  and extremely dense breast , , while with mammography the results are ,  and , .The sensitivity and the specific-ity of ultrasound for dense and heterogeneously dense breast was significantly higher than mammography (P<, ) (, ).Specificity for mammography and subsequent ultrasound for dense breast was , ( of ) and , ( of ), for heterogeneous dense breasts , ( of ) and ,  ( of ) for scattered fibro glandular dense breast , ( of ) and , ( of ) for entirely fatty breast  ( of ) and  ( of ).Ultrasound can be used in the early detection of breast cancer, especially in women with dense breast tissue.

Discussion
Breast cancer, is an important health problem in the Republic of Kosovo.In the last decades there is little increasing of knowledge and development of breast cancer management, which resulted in increasing of mortality rates from breast cancer.All women are at risk for developing breast cancer.Th e older a women is, the greater her chances of developing breast cancer.Approximately  of breast cancer cases occur in women over  years of age.Most important factor in reducing death from breast cancer is early detection.Early detection and treatment is a key to preventing breast cancer from spreading.Mammography and ultrasound are the standard imaging techniques for detection and evaluation of breast disease ().Women who present with breast symptoms or who have palpable findings on clinical examination are usually investigated with breast imaging, which generally consists of mammography or breast ultrasound or both.The choice of primary breast imaging in examining women with symptoms is partly based on age.However, despite the importance of age in clinical practice, little evidence exists as to the appropriate age that delineates the choice of initial diagnostic breast imaging in symptomatic women.In the absence of evidence, experts suggest that women younger than  years be examined with ultrasound, and women  years and older be examined with mammography, as the primary breast imaging modality ().
In our data we show a progressive improvement in sensitivity of mammography in women  years or older relative to younger women, that has been shown in other studies (, , ,).
Overall, the diff erence in the sensitivity of the two tests in all subjects is statistically significant.However, in women  years or younger, ultrasound has a signifi cantly greater sensitivity than mammography.Our study also shows that there is diff erence in the specifi city of the two imaging tests, ultrasound has a signifi cantly greater spec-ifi city than mammography.Th is fact may explain the different fi ndings in published studies, with some reporting a greater specifi city for ultrasound than for mammography (,,,,,,).Ultrasound has long been used as an eff ective diagnostic tool in the evaluation of palpable and mammography abnormalities (, , ).
Although ultrasonography, it is more sensitive than mammography in detecting lesions in women with dense breast tissue (,,,,,,).In young women and women with dense breasts, ultrasound appears superior to mammography.Dense fibro glandular tissue is the most important inherent limitation of mammography in the diagnosis of breast cancer.Bilateral whole-breast US can be an effective adjunct imaging examination in the evaluation of women with dense breast tissue at mammography.

Conclusion
Our results indicate that breast density and age are important predictors of the accuracy of mammography.Breast ultrasound is more accurate than mammography in symptomatic women  years or younger, mammography has progressive improvement in sensitivity in women  years or older.Th e accuracy of mammograms increased as women's breasts became fattier and less dense.In young women and women with dense breasts, ultrasound appears superior to mammography, and may be an appropriate initial imaging test in those women.
EMINE DEVOLLIDISHA ET AL.: COMPARATIVE ACCURACY OF MAMMOGRAPHY ANDULTRASOUND IN WOMEN WITH BREAST SYMPTOMS ACCORDING TO AGE AND BREAST DENSITY

Table 
. shows the comparative sensitivity of the two tests in all subjects and in the different age groups.

TABLE 8 .
Comparative specifi city of mammography and ultrasound in patient with diff erent breast density EMINE DEVOLLIDISHA ET AL.: COMPARATIVE ACCURACY OF MAMMOGRAPHY ANDULTRASOUND IN WOMEN WITH BREAST SYMPTOMS ACCORDING TO AGE AND BREAST DENSITY Sensitivity of both tests in relation to age has variability.The sensitivity of mammography increases substantially after age , ultrasound was more sensitive than mammography in women younger than  years.The ultrasound sensitivity was , , and mammography sensitivity was , (, , , ).