الفهرس 
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Abstract
Neoadjuvant therapy has clinically important outcomes including early treatment of micrometastatic disease, disease downstaging and feasibility of breast conservation in selected cases. Furthermore, NAC may also allow an in vivo assessment of chemosensitivity, potentially allowing a regimen change that would not otherwise be made with traditional postoperative adjuvant treatment. Finally, it provides a platform for important biomarker and correlative studies to enhance our understanding of this disease.
Early evaluation of the treatment response is important to avoid unnecessary therapy in non-responders and to minimize drug-related side effects.
Currently, measurement of breast tumor size (by means of clinical examination, mammography, or ultrasonography) is used to monitor response to treatment. Results of many studies evaluating neoadjuvant chemotherapy in patients with breast cancer have shown that these measurement techniques are imperfect because tumor size changes often become apparent only after several doses of chemotherapy.
The aim of this study was to:
• Evaluate the role of diffusion weighted MRI in assessment of response to NAC as early as one cycle of the chemotherapeutic drugs.
• Assess the role of technique in prediction of tumor response to NAC prior to surgery.
• Evaluate role of diffusion weighted imaging in early prediction of response regarding metastatic nodes.
The study was performed on 20 patients present to the MRI unit of the Radio-diagnosis and Intervention department of Alexandria main university hospital. The patients were referred from the outpatient clinics, diagnosed as breast carcinoma and planned for neoadjuvant chemotherapy. The study was conducted from January 2015 to November 2016.
The patients included in the study underwent:
I. Thorough history taking.
It included patient complain, age, family history of breast cancer or ovarian carcinoma, menstrual history and external hormonal therapy.
II. Complete physical examination.
It comprised general and local examinations. As for the general examination it comprised lymph nodal groups examination (other than axillary nodes), abdominal, skull and spine examination. Regarding the local examination it consisted of clinical estimation of tumor size, site, mobility, lymph node status (enlarged, mobile or fixed) skin (redness, hotness, thickening, dimpling) or nipple (retraction and ulceration) involvement.
III. Mammographic routine views (pre-treatment and post-treatment).
IV. Breast ultrasonography (baseline and follow-up after treatment).
V. Histopathological assessment by tissue biopsy (for diagnosis, and after surgery) and immunohistochemistry.
VI. Magnetic resonant mammography (MRM)
MRI was done for all patients at three time points. The pre-treatment and post-treatment studies entailed T2 fat saturation, T1 non-fat saturation, DWI-MRI and T1 post-contrast dynamic sequences. A study after the 1st NAC was done and entailed T2 fat saturation and DWI sequences.
In DWI, b values of 0, 400 and 800 were used. In post-examination processing multiple ROI technique was used. In a trial to achieve standardized conditions for results analysis and avoiding data contamination by adjacent structures, multiple freehand regions of interest (ROI), with mean area of 30 mm2 (ranging from 10 to 50 mm2), were individually placed on the ADC map at the site of the target lesion and the minimum (ADCmin), mean (ADCmean) and maximum (ADCmax) ADC values were calculated. Necrotic or cystic components were avoided.
As for DCE-MRI, time intensity curves were calculated at the pre-treatment and post-treatment studies.
Several risk factors for breast cancer have been assessed e.g old age, family history and parity.
The most frequently affected quadrant was the UOQ (45%) followed by the LIQ (15%).
Pre-treatment mammography showed single breast mass (60%), architecture distortion (20%), suspicious calcifications (20%), breast asymmetry (10%), skin thickening (20%) and multiple masses (15%).
Post-treatment mammography of the 19 patients who completed the study demonstrated complete disappearance of the lesions in 2 patients (10.5%). In the remaining 17 patients (89.5%) mammography showed persistent malignant features comprising persistent mass shadow in 13 patients (68.4%), micro-calcifications in 4 patients (21%), architecture distortion in 4 patients (21%), asymmetrical density in 2 patients (10.5%), and skin thickening in 2 patients(10.5%).
Pre-treatment ultrasonography detected suspicious masses in 19 patients (95%) all of them showed suspicious morphology and architecture distortion in a single patient (5%). Ultrasound gave false positive diagnosis of multifocal breast cancer in 2 patients that has been correctly diagnosed as single large breast mass by MRI. As for the axilla, ultrasound misdiagnosed 4/13 metastatic lymph nodes as normal. Second-look ultrasound after MRI examination coincided with the morphological changes depicted by MRI.
Follow-up sonography after the 1st NAC cycle showed no significant changes regarding the breast mass morphology. Five/13 metastatic axillary nodes regained their normal ultrasound morphology.
Post-treatment ultrasound showed two (10.5%) out of 4 patients reported by MRI as complete response on sonographic bases. The other 2 patients were misdiagnosed as partial response and showed an area of architecture distortion. Collectively, pre-operative ultrasound examination showed 10 patients (52.6%) with partial response and 7 (36.8%) with stable disease (non-responder) (including the patient presented sonographically with architecture distortion).
On Pre-treatment MRI study, conventional MRI correctly diagnosed all 19 masses as malignant. Their location coincided with that depicted by ultrasound. One patient was diagnosed as multifocal breast carcinoma (5%). Assessment of the pre-treatment mass size of the breast masses examined proved to be of statistically significance when correlated with response to NAC.
DCE-MRI classified BPE in 20 patients as follow: 9 patients (45%) were classified as type II, 8 patients (40%) as type III and 3 patients (15%) as type IV. Two non-mass enhancement (NME) were diagnosed. One of segmental asymmetrical heterogenous type and the other was of linear clumped morphology. As for pre-treatment dynamic curve, only one mass (5%) with IDC showed type I (progressive) curve.Two masses (10%) showed type II (plateau) curve and 17 lesions (85%) showed type III curve.
Conserning the pre-treatment DWI-MRI all examined masses showed restriction with ADCmin-ADCmax value of 0.80 – 1.10 × 10−3 mm2/sec (ADCmean value of 0.98 ± 0.09× 10−3 mm2/sec). Among the two lesions expressing NME in DCE-MRI, one of them showed restrictive pattern with ADC value of 1.1× 10−3 mm2/sec. The other (segmental NME pattern) could not be detected on DWI-MRI with ADC value of normal breast parenchyma(1.6× 10−3 mm2/sec). The pre-treatment metastatic lymph node ADC showed ADCmin-ADCmax value of 0.66-1.33× 10−3 mm2/sec (ADCmean value of 1.06± 0.18× 10−3 mm2/sec). ADC value had neither correlation with the molecular subtypes of the tumor nor development of associated axillary lymph nodal metastasis. Neither the pre-treatment BPE, various DCE curves types, ADC values or molecular mass type showed statistical significance on correlation with neoadjuvant treatment response.
MRI examination 7-9 days after the 1st NAC cycle treatment showed no significant primary breast mass morphological changes including size on conventional MRI study. On the other hand 5/13 lymph nodes regained their normal morphological shape.
The DWI-MRI examination done 7-9 days after the 1st NAC cycle, showed water diffusivity increase in both responder and non-responder groups with variable degrees. 27% increase in ADC value is required for the breast mass to regress more than 30% in maximum diameter after NAC (radiological response). The metastatic lymph node ADC showed non-significant ADC values. Their ADCmin-ADCmax value were 0.8-1.30× 10−3 mm2/sec (ADCmean value of 1.07± 0.18× 10−3 mm2/sec).
The post-treatment MRI study showed complete radiological (MRI) response in 4/19, partial response in 9/19 and stable disease in 6/19 patients.
Conventional MRI study showed increase the percentage of the shape irregularity (92.8% in the post-treatment study to 63% in the pe-treatment one), and tumor necrosis (28.5% in the post-treatment study to 10.5% in the pe-treatment one). Mass size showed regression with a mean of 2.93 ± 2.41cm instead of 4.88 ± 2.19 cm in the pre-treatment study.
DCE-MRI showed increased masses heterogenity on enhancement (85.7% in the post-treatment study to 68.4% in the pe-treatment one). Two patients (14.3%) showed fragmentation sign. Compared to pre-treatment study, the post-treatment study showed significant change of the BPE among the 19 cases who completed their NAC program. Conserning the time intensity curve changes, out of 16 lesions that showed type III curve in pre-treatment DCE-MRI assessment, 6 changed to type I curve, 6 showed persistant type III curve (including the NME patient) and 4 turned to type II curve after NAC treatment. Both of the 2 masses who showed type II curve in the pre-treatment study expressed type I curve after treatment. The single mass that showed pre-treatment type I curve showed stationary type I curve after treatment. However these changes were statistically insignificant.
As for the DWI-MRI, the post-treatment mass ADC values were found to be increased. The ADCmin-ADCmax reached 1.0 – 1.70 × 10−3 mm2/sec, and the ADCmean reached up to 1.28 ± 0.22× 10−3 mm2/sec.
The current study results showed good agreement between radiological (MRI) and pathological responses.