Breast-conserving treatment has allowed many women to receive appropriate breast cancer management with long-term local control and survival rates equivalent to those with mastectomy, while maintaining a cosmetically acceptable breast appearance. Unfortunately, women with larger breasts can be technically challenging to treat with breast irradiation, resulting in higher rates of severe acute dermatitis and late fibrosis causing unacceptable cosmesis. Our institution has developed prone breast 3D-CRT to improve these toxicities in this patient population. We have previously evaluated patient positioning when prone and demonstrated that minimal anterior–posterior movement occurs (17
). The positioning and the use of 3D-CRT planning have allowed us to treat patients without consideration of lumpectomy cavity location. The association of dosimetric parameters with toxicity and cosmetic outcomes is the subject of a separate manuscript. Using prone 3D-CRT for WBI in a population with high BMI and/or large pendulous breasts, we have demonstrated acceptable acute and late toxicities, with cosmesis rates comparable to those observed in supine series that included patients with smaller breast and body size.
Several authors have published data indicating worse cosmetic outcomes and toxicities for those with increased weight (7
), higher BMI (9
), and larger breast size (2
). The cosmetic outcomes of the largest breast volumes in our study (>1200 cm3
, 60% of our patients) are compared with a subset of these studies in . Clarke et al.
) examined 78 cases of supine two-dimensional radiotherapy (2D-RT) for WBI and found 100% excellent cosmesis in patients with A cup size, as opposed to only 50% of those patients with ≥D cup size (p
=0.02). Cosmesis was also associated with patient body weight: 90% of patients weighing <120 lb had excellent outcomes, as opposed to only 46% of patients weighing >120 lb (p
=0.001). Ray et al.
) examined the influence of breast size on late radiation effects in 130 patients receiving supine 2D-RT WBI. Those with an A or B cup size had 92% excellent cosmesis, vs. only 64% of those with ≥C cup size. Moody et al.
) monitored late radiation changes in 664 women undergoing supine postlumpectomy WBI. They found moderate or severe late radiation changes in 6% of patients with small breasts, vs. 39% of those with large breasts (p
< 0.001). Gray et al.
) from Memorial Sloan Kettering Cancer Center (MSKCC) specifically looked at the cosmetic outcome of large breasted or heavy women treated supine. A total of 257 patients were divided into a “large” group if weight ≥80 kg, bra size ≥40 in, ≥D cup size, or if tangent separation ≥23 cm. They found a significant difference in cosmesis at 1 and 3 years and a trend toward improved outcomes with “average” patients at 5 years. Of the factors considered in the cosmesis score, retraction and symmetry were statistically significant at 5 years. In the present study, we report good to excellent cosmetic results in 89% of our patients with large and/or pendulous breasts receiving 3D-CRT in the prone position after BCS. This rate of good to excellent cosmetic outcomes is similar to those reported in patients treated supine (22
). For example, a Phase III randomized study examining 2D-RT vs. intensity-modulated radiotherapy (IMRT) for supine WBI found that 85–95% of patients in both treatment groups had no or mild changes in the breast appearance at 2 and 5 years. These patients had a median breast volume of 1046 cm3
, much lower than our median breast volume of nearly 1400 cm3
Physician-assessed cosmetic results from breast-conservation therapy in large and/or pendulous breasts
There is growing literature regarding the use of prone positioning to improve toxicity profiles from irradiating large– pendulous breasts after BCS. Treated supine, women with larger breasts have increased dose heterogeneity, and excess skin folds can create a bolus effect in the inframammary and axillary areas. Prone breast irradiation minimizes separation of the breast tissue and reduces skin folds. The MSKCC has the largest and longest documented study using the prone position for 2D-RT WBI. Cosmetic outcomes were initially reported for 59 patients after a median follow-up of 38 months (27
). The population had a median bra size of 41D. Mean cosmetic outcome for the entire group was quite favorable, with a score of 9.37 (out of a total of 10). This group subsequently reported late toxicity on 245 patients treated in the prone position (28
). In that series, late Grade 2, Grade 3, and Grade 4 chronic dermatitis was seen in 27.8%, 2.8%, and 1.6% of patients, respectively, with Grade ≥2 chronic edema in 14% of patients. Similarly, Formenti et al.
) treated 91 patients of all sizes in the prone position using accelerated IMRT as part of a Phase I/II trial, and with 12 months median follow-up reported favorable acute and late toxicities corroborating the prone position’s favorable effect on toxicity.
Our patient population had a high median BMI of 33.6 kg/m2
and median breast volumes of nearly 1400 cm3
and yet had favorable acute toxicity profiles (). Only 4.5% had Grade ≥3 acute dermatitis, with 16% of patients experiencing any moist desquamation and only 2% of patients experiencing moist desquamation outside the inframammary folds. These results seem favorable when compared with a Phase III trial examining acute toxicities from IMRT vs. 2D-RT for supine WBI (30
). Those patients had a smaller average size than the patients in our series, with a mean BMI of 27 kg/m2
and median breast volume of 973 cm3
receiving 95% of the prescribed dose, yet 27.1% had Grade 3 to 4 skin toxicity, and 31.2% experienced moist desquamation in the IMRT arm. Other studies including all sizes of patients have also demonstrated moist desquamation rates of 14–38% (31
). In our series of patients with larger body habitus and/or large– pendulous breasts, the overall rate of Grade ≥2 late toxicity was 11.4%, and Grade ≥3 was 1.9% (). Grade 1 fibrosis and hyperpigmentation were the most common late toxicities. It is difficult to compare retrospective studies given institutional differences in patients, treatments, analysis methods, physician evaluations, and biases. However, it seems that these rates of late toxicities represent significant reductions compared with what was reported previously for patients with large breast or body habitus receiving breast radiotherapy in the supine position (2
). Most importantly, in our analysis, as discussed below, our patients with the largest BMI and breast sizes did not experience worse fibrosis or poorer cosmetic outcomes from radiation.
We sought to specifically evaluate the effect of breast size and BMI on the incidence of acute and late toxicities as well as cosmesis from prone breast radiotherapy in this population. Assessing breast size proved challenging because most other series have used patient brassiere cup size (4
). There is not an industry standard matching volume of breast to cup size. Bra cup size is relative to the band size, with actual cup volume changing as the band size changes. For example, the brassiere cup volume is the same for 30D, 32C, 34B, and 36A (34
). Inconsistency can also occur if a woman wears a bra size too large or too small. Therefore, we elected to use CT-based breast volume as a discriminator for breast size. Examining acute toxicities in our study demonstrated that use of prone 3D-CRT resulted in neither BMI nor breast volume being significantly associated with Grade ≥2 dermatitis. However, larger BMI and breast volume were significantly associated with moist desquamation, and BMI was also associated with breast pain during treatment (). We now use this information to more aggressively monitor and treat acute side effects in these patient groups during treatment. Additionally, larger breast volume and BMI were not associated with worse late toxicities, specifically fibrosis, nor with lower rates of excellent to good cosmesis (). This supports our hypothesis that the use of 3D-CRT WBI in the prone position eliminates these factors as predictors of poor outcome. As has been demonstrated by others (16
), the use of chemotherapy was associated with higher rates of fair to poor cosmetic outcomes.
With a median follow-up of 40 months, we had 4 patients (3.0% 5-year rate) with an ipsilateral cancer recurrence. This is within the expected recurrence rate for BCT for early-stage breast cancer (28
). Of note, all of these patients had a BMI greater than the median BMI of 33.6 kg/m2
. Further characterization and follow-up of the recurrence patterns relative to BMI will be reported separately.
This analysis has limitations inherent to retrospective studies, such as the potential for reporting bias. It is possible that those lost to follow-up had different outcomes; however, this accounts for only 4.5% of patients (n =5). Our study uses the well-established combination of the National Cancer Institute Common Terminology Criteria for Adverse Effects Version 3.0 and the Harvard Cosmetic Scale for physician-assessed cosmesis and late toxicities that can affect breast appearance. We recognize that the best evaluator of cosmetic and toxicity outcomes is the patient herself and acknowledge that one of the weaknesses of this study is the lack of patient-rated outcomes. However, our study strengths include that the population is specifically focused, that toxicity and cosmesis were scored prospectively, and that the median follow-up is sufficiently long to take into account the latency of radiation toxicities.
In conclusion, the delivery of whole breast radiotherapy using 3D-CRT in the prone position resulted in excellent acute and late toxicity profiles for a patient population at the highest risk for toxicity from breast irradiation. We also report that 89% of patients had good to excellent cosmetic outcomes. We did not find an association between BMI or breast volume and late fibrosis or cosmetic outcomes, indicating that prone whole-breast 3D-CRT eliminates BMI and breast volume as factors predicting poorer late toxicity and cosmesis. This gives further evidence that prone positioning for WBI is preferable to supine in this patient population.