In this study, we have measured different currently used breast oedema criteria and evaluated a new objective diagnostic measurement tool for parenchymal breast oedema, prior to BCS and following RT. HFUS images and US elastography images were obtained in four quadrants of both the operated and non operated breast of 20 patients. We have compared baseline results with follow-up measurements and the operated with the non operated breast. Possible risk factors and correlations between breast oedema criteria have been investigated.
of the operated breast, rated by the patient, was present in almost half of the patients following RT. Subjective breast oedema following RT, rated by an experienced breast radiotherapist and physical therapist (NA), resulted in respectively at least grade one skin toxicity and clinical breast oedema in all patients.3
Subjective symptom rating by patients and clinicians are not satisfying for the diagnosis and degree of parenchymal breast oedema.
of the operated breast following RT was over 2 mm in all patients and significantly thicker than prior to surgery, unlike the non operated breast skin. Skin thickness of the operated breast following RT was significantly thicker than the non operated breast, unlike preoperative results. Skin thickness increase is caused by an increased extravascular-extracellular leakage space in the (hypo)dermis and extensive cellular fibrosis, characterized by the loss of consistent pattern in extracellular structures.16
Mean total cutaneous thickness was 2.71 mm in an operated and irradiated breast and 1.35 mm in a non operated/irradiated breast. This difference was significant.6
Mean skin thickness of the operated breast following RT in our study was 3.03 mm and 1.64 mm in the non operated/irradiated breast, which is similar to the results of Wratten et al
. (1.36 mm increase versus 1.39 mm increase following BCS and RT).6
These results show that skin thickness increase over 2 mm following BCS and RT is a reliable diagnostic criterion for cutaneous breast oedema.
Echogenicity of the subcutis in the operated breast following RT increased in 89.5% of the patients and was significantly higher than prior to surgery, unlike the non operated breast subcutis. Echogenicity of the subcutis of the operated breast following RT was significantly higher than the non operated breast, unlike preoperative results. Increase in echogenicity of the subcutis reflects a hypoechoic area.
Increased echogenicity of the subcutis in the operated breast following RT can be caused by an increased subcutaneous extravascular-extracellular leakage space.16
Parenchymal breast oedema might also be the result of a manifestation of an increased number of perfused microvessels, persistent microvascular leakage, impaired drainage, and loss of architectural integrity of tissue microstructures related to radiation-induced vascular injury.16
Our study results could not be compared with other literature results, because echogenicity depends on the gain used on the HFUS exams, frequency of the probe, tissue characteristics, location on the breast and follow-up time. However, 85% of the patients with BCS and RT had an increase in breast tissue density in the study of Delay et al
.; and Ronka et al
. also observed an increased echogenicity.11
Wratten et al
. described a decrease in echogenicity of the subcutis following BCS and RT.
In our study HFUS settings were standardized, so we can conclude that there was a significant increase of the echogenicity of the subcutis, most likely due to the presence of oedema in the subcutis. Like skin thickness, echogenicity of the subcutis can be a valuable diagnostic criterion, when taking into account standardization of methodology as previously described.
Visibility of the echogenic line in the subcutis of the operated breast following RT decreased in all patients and was significantly lower than prior to surgery, unlike the non operated breast. Visibility of the echogenic line in the subcutis of the operated breast following RT was significantly lower than the non operated breast, unlike preoperative results.
These results are similar to the results of Ronka et al.11
This criterion is subjectively scored, by only one experienced breast radiologist (DB) for all measurements in all patients. Visibility of the echogenic line in the subcutis of an operated breast following RT decreases, because of disturbance of the skin/subcutaneous fat interface due to presence of cutaneous and subcutaneous oedema. Therefore visibility of the deeper echogenic line can also be a useful diagnostic criterion for assessing breast oedema.
Mean interstitial fluid accumulation
of the operated breast following RT increased in 72.2% of the patients and was significantly higher than prior to surgery, unlike in the non operated breast. Interstitial fluid accumulation of the operated breast following RT was significantly higher than the non operated breast, unlike preoperative results. These results were not significantly higher in the upper quadrants of the operated and irradiated breast. This could be explained by the influence of gravity on the fluid in the breast. Presence of interstitial fluid accumulation in the operated and irradiated breast is an objective HFUS visible entity. It is a valuable diagnostic criterion for presence of interstitial oedema due to fluid leakage in the extracellular interstitial space. Our study results are similar to the results of Ronka et al.
and Wratten et al.
who also observed an increased interstitial fluid accumulation in the operated and irradiated breast.11
Mean elasticity ratio of the subcutis of the operated breast following RT increased in 88.9% of the patients and was significantly higher than prior to surgery, unlike the non operated breast. Mean elasticity ratio of the subcutis in the operated breast following RT was significantly higher than the non operated breast, unlike preoperative results. These results were not significantly higher for all quadrants of the operated and irradiated breast. Our group compared the strain of the subcutaneous fat tissue with the strain of an elastic gel pad giving an elasticity ratio. Increase in elasticity ratio in the operated and irradiated breast corresponds to more elastic breast tissue in comparison with the preoperative results. An increase in elasticity of the underlying breast tissue could be explained by the increase of fluid in the breast. Our study results could not be compared with other literature results, because to our knowledge, no other research group has used the same methodology.
Elasticity ratio can be a valuable diagnostic criterion, when taking into account standardization of methodology. Although elasticity ratio in the different quadrants of the operated and irradiated breast was higher than baseline measurements and the non operated breast, the difference was not significant. Further research with more patients is necessary to confirm these results.
between different breast oedema criteria were present between mean elasticity ratio and mean visibility of the echogenic line in the operated and irradiated breast only. Wratten et al.
found a correlation between subjective parenchymal breast oedema and skin thickness and between skin thickness and cutaneous echogenicity.6
The absence of other correlations with our new technique could suggest elasticity ratio to be a supplementary criterion for the diagnosis and degree of breast oedema, giving extra information on hydrated breast tissue elasticity. Additionally, making a combination of the four breast oedema criteria, measured with HFUS the incidence of breast oedema was 90.4% following RT, compared to 88.9% with increased elasticity ratio.11
The breast oedema definition and our new technique result in equal incidences.
Unlike similar research, we did not found risk factors
for the increase of parenchymal breast oedema, expressed by increased elasticity ratio in this study, except for bigger preoperative bra cup size.3
All patients had an increased mean elasticity ratio in the operated and irradiated breast, except for patients with preoperative A cup.
Echogenicity and elasticity ratio were obtained from the subcutis and not cutaneous, because breast skin behaves different than the underlying breast tissue and literature showed disagreement on cutaneous measurements.6
Measurements in the inframammary fold of the operated and irradiated breast were not discussed in this manuscript, as well as measurements of the first follow-up (postoperative but prior to RT) for the same reasons.
Our study presents several limitations. Our pilot study counts only 20 patients and a short follow-up. As part of the institution’s surgical management, operated breast cancer patients receive a prescription for ambulatory physical therapy at the time of discharge. However, we did not record the compliance of patients or their receipt of manual lymphatic drainage of the breast during the study, although their beneficial effects on breast oedema could be expected.34
Another limitation of our study is the known lack of reliability of breast oedema criteria measurements. Our study results should be interpreted with these restrictions in mind.
One strength of the study is standardization of HFUS settings, US elastography methodology and measurement protocol, like gain, gauges, etc. by a specialized breast radiologist (DB). Gain was often adjusted to become better clinical results in other studies, but this was not the case in our study.6
Wratten et al.
concluded that HFUS was not useful in quantifying acute inflammatory changes induced by breast irradiation, but with our standardized approach this was possible.14
A second strength of the study is the preoperative measurements to compare with immediate post irradiation measurement. To our knowledge, no other research groups have used preoperative bilateral measurements as baseline results. Another strength of our study is that the trial was conducted in a single institution. All patients were followed by the same team, which ensures that assessments were consistently performed throughout the trial. We believe that the strengths of the study outweigh its limitations and that the results are robust, at least within the current short follow-up time frame.
Because this is a pilot study, the long-term usability of this technique cannot yet be demonstrated; however, this technique seems to be an interesting quantitative objective complement to current breast oedema diagnostic criteria. A follow-up of six months and one year following surgery is scheduled as part of the study, like the time course of parenchymal breast oedema during and following RT was previously described by Wratten et al
Breast oedema incidence peaks at four to six months following treatment and returns to baseline after one year. It will be interesting to see if changes, observed in this analysis are confirmed at later follow-up. Our findings suggest further investigation with more patients and longer follow-up.
We can conclude from our study results that ultrasound elastography is an objective quantitative measurement tool for the diagnosis of parenchymal breast oedema, in combination with other objective diagnostic criteria.