Summary:

MATERIALS AND METHODS

An open, multicenter study was conducted across 6 centers (France and Sweden) in eligible women (brassiere cup size, A/B) aged 25–60 years. Subjects received an injection of up to 100 mL of HA gel (Macrolane VRF30, Q-Med AB, Uppsala, Sweden) into each breast (between the glandular tissue and the pectoralis major muscle fascia), according to the instructions for use, after local anesthetic. A subgroup was offered retreatment 9 months later. Touch-up treatments of up to 20 mL per breast were permitted after initial treatment and retreatment in cases of unevenness and/or asymmetry. The study was performed in accordance with the Declaration of Helsinki and approved by local ethical committees. Subjects provided written informed consent.

Degradation and localization of HA gel was assessed by magnetic resonance imaging at baseline and 12 and 24 months after a single injection or at baseline; 6 months after initial injection; 0–2 weeks before retreatment; and 6, 9, and 15 months after retreatment.

Safety was assessed by adverse event (AE) reporting (baseline to 24 months after the last treatment). Expected AEs (bruising, itching, nodules, pain, redness, swelling, and tenderness), other AEs, and use of concomitant medications were recorded in subject diaries 14 days after initial treatment and/or retreatment. Mammography and ultrasonography were performed at screening and 24 months after initial treatment.

The primary endpoint was the proportion of breasts improved (baseline to 6 months after initial treatment) as assessed by the subject (single-treatment and retreatment groups combined) using the Global Esthetic Improvement Scale (GEIS). Subject satisfaction was a secondary efficacy endpoint.

All subjects who received the study product were eligible for safety and efficacy assessment. For the primary endpoint, 95% binomial distribution-based confidence intervals were used. Comparisons between single-treatment and retreatment groups were performed using a 2-sample t test.

RESULTS

Seventy-one subjects received an initial injection of HA gel, and 22 subjects underwent retreatment (Table ​(Table11).

Table 1.

Demographic and Injection Data, ITT Population

Adverse Events

In the single-treatment group, 127 AEs in 33 subjects were considered related to HA gel or injection procedure; 96% were of mild-to-moderate intensity, and most (87%) did not require intervention (Table ​(Table2).2). One subject had a serious AE (implant-site bacterial infection caused by Peptostreptococcus species), judged to be related to the injection procedure but not to the study product. The breast was drained, and the infection was treated with antibiotics. There was some residual scarring at the incision site. Common AEs included implant-site nodules (n = 15), medical device implantation events (ie, perception or unevenness of the study product; n = 13), and capsular contracture (n = 11). These AEs were judged to be of mild-to-moderate intensity, had a mean time to onset of 2–5.5 months, and resolved within 3–10 months.

Table 2.

Summary of Reported AEs

In the retreatment group, 70 AEs in 20 subjects were considered related to the study product or injection procedure; 46 occurred in the 24 months after retreatment. Over the 24-month follow-up for the retreatment group, 92% of treatment-related AEs were mild to moderate, and 70% did not require intervention (Table ​(Table2).2). Two subjects had serious postoperative implant-site infections after retreatment. One case (caused by Staphylococcus aureus) was severe and judged to be related to the injection procedure but not to the study product; the other case of infection could not be determined, was of moderate severity, and was judged to be related to the study product and injection procedure. Both subjects were treated with antibiotics. Common AEs included implant-site nodules (n = 14) and injection-site nodules (n = 9). These AEs were judged to be of mild-to-moderate intensity and had a mean time to onset of 2–3 months after initial treatment, 3–9 months after retreatment, and with the exception of 1 subject (mild injection-site nodules), and all AEs had resolved by 24 months.

GEIS Assessments

Overall (both groups combined), 85.5% of breasts (95% confidence interval: 78.0––91.2) were improved according to the subject GEIS 6 months after initial treatment (primary endpoint; Fig. ​Fig.1).1). Corresponding percentages for investigator and independent evaluator assessments were generally higher compared with subject assessments (data not shown).

Fig. 1.

Percentage of improved breasts as assessed by the subject using GEIS in the single-treatment group and the retreatment group. * indicates P < 0.05 compared with the corresponding time point after initial treatment (retreatment group); † ...

The percentage of breasts rated as improved by subjects, 24 months after last treatment, was comparable between treatment groups (P = 0.473).

Subject Satisfaction

In total, 98% of single-treated subjects reported satisfaction with their breasts in general, 6 weeks after treatment, compared with 32% of subjects before treatment (Fig. ​(Fig.2).2). All retreated subjects were satisfied with their breasts in general up to 3 months after initial treatment, compared with 36% of subjects before initial treatment (Fig. ​(Fig.2).2). There was no significant difference in subject satisfaction between treatment groups, 24 months after last treatment.

Fig. 2.

Percentage of subjects who were satisfied (satisfied was defined as “mostly satisfied,” “very satisfied,” or “completely satisfied”) with their breasts before and up to 24 months after the initial treatment ...

DISCUSSION

This is the first long-term evaluation of gel degradation, safety, and aesthetic outcomes after 2 injections of HA gel for breast enhancement. These findings indicate that gel degradation was not complete in any subjects, 24 months after last treatment. Additionally, HA gel can obscure breast tissue on screening mammography, which can be overcome through a combination of digital mammography and ultrasonography.

Treatment with HA gel was associated with subject-assessed improvements in breasts at 6, 12, and 24 months. Retreatment significantly improved subject GEIS assessments and satisfaction, 12 and 24 months after initial treatment. There was no difference between treatment groups 24 months after the last treatment, reflecting the product’s biodegradable nature. Treatments were received at the study start; a weak incentive to return may account for the subjects lost to follow-up. Nevertheless, these follow-up data should guide physicians on the appropriate care after breast enhancement with HA, with information from longer-term follow-ups recommended.

The time of onset for most AEs was less than 6 months, with severity mild to moderate, and the majority had resolved at 24 months, even though HA gel was still present. Three subjects developed infections, despite antiseptic wash before treatment. Therefore, additional preventive measures to reduce the risk of infection should be considered.

In conclusion, although single treatment and retreatment of HA gel were generally well tolerated, physicians should be aware of common and more serious treatment-related complications (eg, infection) and the need for adjunctive ultrasonography when doing mammography screening.

ACKNOWLEDGMENTS

The study was funded by Galderma, who provided Macrolane VRF30. Medical writing services were provided by Louisa Pettinger, PhD, of Fishawack Communications Ltd, funded by Galderma.

Footnotes

REFERENCES