Novel Paradigm for Treating Idiopathic Granulomatous Mastitis

Idiopathic granulomatous mastitis (IGM) has a high prevalence in Asia and Africa[1]. It usually presents as a tender mass with rapid progression and has a recurrent or prolonged natural disease course that eventually leads to lesion burnout [2]. Severe cases usually have multiple simultaneous foci of abscesses with overlying skin inflammation and ulceration. Nipple retraction, sinus formation, peau d’orange-like changes and axillary adenopathy are also common accompanying symptoms [3]. Until recently, the etiology of IGM was unclear, and it was generally regarded as a kind of inflammatory disease that may be related to autoimmune disorders, trauma, hyperprolactinemia and Corynebacterium infection [4,5].

Before the 1980s, most patients with IGM were treated exclusively with wide surgical excision. More recently, conservative therapy with oral steroids or imaging surveillance was endorsed as a first-line treatment option before surgical consideration [6]. However, both of the above treatments have their own drawbacks. Steroid therapy is usually associated with a high recurrence rate. The treatment usually lasts up to 12 months [7], and some refractory diseases may eventually require surgery. Additionally, given the long-lasting natural disease course of IGM, long-term steroid treatment may cause severe adverse effects such as hyperglycemia, osteoporosis and infection. On the other hand, surgery can cause scar formation, nipple retraction and substantially compromise the breast contour, especially for patients with large lesions. Previous studies argued that surgery is not effective in IGM management due to its high risk of recurrence and extensive scarring compared to steroid treatment with abscess drainage [8]. Until recently, the optimal treatment for IGM remained unclear.

In the study by Wang et al., the authors investigated a new therapeutic paradigm involving treatment with a combination of both steroids and surgical excision [9]. Up to 200 IGM patients with severe local symptoms (presented with at least two abscesses with skin rupture and all lesions were >5 cm) were recruited to receive 5 days of treatment with glucocorticoid and levofloxacin. Then the participants were allocated to either the steroid or surgery group. Patients benefited from surgical treatment in terms of reduced wound healing time (Surgical vs. Nonsurgical: 25 vs. 258 days), a lower recurrence rate (Surgical vs. Nonsurgical: 5.1% vs. 22.7%) and better cosmetic effects.

This study provides insights into IGM management. The key points for IGM management lie in preventing recurrence and improving cosmetic effects as well as quality of life. IGM is generally divided into acute and chronic stages. The acute stage of IGM usually has a rapid progression, developing from skin redness to a 5-cm tender mass in just a few days. The chronic stage usually presents with recurrent abscesses and persistent fistula formation. Both surgery and conservative therapy with steroids have their own pros and cons in different disease stages. For instance, systemic steroid treatment can be very effective in the acute stage, with significant relief of local inflammatory symptoms leading to mass shrinkage. However, in chronic stages, the chronic abscess with a thick capsule and fistula usually does not respond well to glucocorticoid treatment, and the patients may need long-lasting medication for up to 1 and 2 years. Alternatively, surgery with wide local excision and thorough debridement could be very effective in eliminating chronic inflammatory lesions and preventing recurrence, but in the acute stage, it could require removal of bulky breast tissue and has a high rate of recurrence and surgery-related complications. The present study describes a novel paradigm combining surgery and steroid treatment, which could lower the recurrence rate to 5.1% and largely shortens the duration of steroid administration [9].

This combination strategy also has other advantages. First, it preserves more breast tissue to achieve better cosmetic effects. The anti-inflammatory effects of steroids could slow down the progression of IGM and confine the lesion to a relatively small area, which could be helpful to the plastic procedure after wide local excision. Second, this modality could potentially reduce IGM recurrence by better delineating the boundary between granulomatous tissue and normal breast tissue, which facilitates thorough surgical debridement. In the acute phase of IGM, it is sometimes difficult to differentiate between granulomatous tissue and edematous normal breast tissue, and any granulomatous tissue left could result in rapid local recurrence and even widespread in-breast disease. Pre-op steroid treatment could help to delineate the border of the inflammatory lesion and achieve en bloc resection with clear margin.

The present study also provides several new directions for optimizing the current IGM treatment protocol. First, the authors administered pre-op steroids for five days. This may be useful to stabilize the disease, but the optimal duration for pre-op steroid treatment remains unknown. A longer duration may be more helpful to shrink the inflammatory lesion. Second, the response to pre-op steroid treatment and other inflammatory indicators could be potential prognostic indicators to further evaluate whether surgery could be omitted to deliver personalized treatment. A risk model could be developed to stratify patients into different recurrent risk subgroups to determine who should receive either steroids or surgery alone, or even merely observation. Third, further evaluation is worthwhile to determine whether continuation of steroid treatment after surgery could result in a lower recurrence rate. Given the adverse effects of long-term systemic steroid treatment, several ongoing clinical trials are focusing on topical steroids and local injection to minimize side effects and avoid surgery (ClinicalTrials.gov Identifier: NCT03766997, NCT02959580). Further large-scale clinical trials are warranted to implement personalized and precise protocols for IGM treatment.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by Key Projects in the National Science and Technology Pillar Program during the Twelfth Five-year Plan Period; Beijing Municipal Science and Technology Project.