Reduction Mammoplasty is Beneficial in Women with and Without History of Breast Cancer

“In comparison to age-matched women, those with breast reduction for macromastia were found to have subsequent lower frequency of breast cancer.”

Hypertrophy of breast (macromastia and gigantomastia) is defined as an increase in the weight of the breast which exceeds the physiologic limit. No consensus definition on how excess is excess to qualify for macromastia. However, 1.5 kg (3.3 lb) may be considered as a cutoff between physiologic and morbidly enlarged breast [1]. Surgical intervention by reduction mammoplasty is usually the treatment of choice especially in the western countries. In addition to the cosmetic effect, breast reduction is frequently performed as a risk reducing procedure in patients with a personal or family history of breast cancer [2,3].

Histological evaluation of the reduction mammoplasty specimens

It has been reported [4–6] that histological examination of excised breast tissue is an important parameter for detecting any abnormality. The excised tissues must be morphologically evaluated following established criteria [4]. These criteria determine the normal architecture of the breast by normal ducts and lobules and state that no significant pathological changes are present in these specimens. The morphology must be correlated with the age, menopausal and parity status [5]. It has been shown that the breast tissue from premenopausal nulliparous women is characterized by predominance of fibro-adipose tissue relative to less terminal lobular units. The glandular parenchyma is formed mainly by ‘lobules type 1’ as opposed to the breast tissue from premenopausal parous women in which the fat is significantly less prominent and the interlobular stroma separates ‘lobules type 3’. In general, the glands of nulliparous women are mainly composed of ‘lobules type 1’, whereas the tissue of parous women is mainly formed by ‘lobules type 3’ [6].

Occult breast cancer in reduction mammoplasty specimens

The reported incidence of an occult (incidental) breast cancer in reduction specimens has ranged from 0.06 to 4.6% in patients with no history of breast cancer [7,8]. On the other hand, patients with history of breast cancer have a two- to six-times increased risk of developing another primary in the contralateral breast [9]. The reported rate is even much higher (12–19%) in patients with BRCA1 or BRCA2 germline mutation [10]. Pathologic examination of reduction mammoplasty specimens is a must to document any occult breast cancer or other atypical proliferative lesions (APLs). Some patients may feel disadvantaged as a result of identifying an occult malignancy in the reduction specimen. This may indicate the necessity for preoperative counseling and screening mammography to identify any masses, calcifications or architectural distortion to minimize the risk of undiagnosed invasive disease being suspected preoperatively.

The prevalence of APLs in reduction mammoplasty specimens in patients with no history of breast cancer

The incidence of invasive carcinoma and ductal carcinoma in situ (DCIS) in reduction mammoplasty specimens varies [11,12]. This variation however may be due to the inclusion criteria of cases in different studies. This includes, but not limited to, personal and family history of breast cancer, presence of known BRCA germline or somatic mutation beside others. It is well known that breast cancer is more frequent in older age group [13] and reduction mammoplasty is frequently performed in relatively young women with macromastia [14]. Therefore, inclusion of young patients, which constitute a good proportion of cases where breast reductions are performed, may underestimate the frequency of APLs in multiple studies [8].

In our study, among 2498 cases of reduction mammoplasty with no history of personal breast cancer, the vast majority (98.6%) had bilateral reduction for macromastia and the remaining 1.4% of cases had unilateral reduction mainly for cosmetic reasons and to treat breast asymmetry [8]. Among those 2498 cases, 107 (4.3%) were diagnosed with APL. One of the most important factors that correlates with the presence of APL is the patient's age. The presence of APL has been significantly lower (0.6%) in patients <40 years compared with 7.5% in those aged >40 years with an odds ratio of 0.2 (p < 0.001) [8]. Many others concluded that the likelihood of diagnosing APL in reduction mammoplasty specimens increases in advanced age [11,15].

The prevalence of APLs in reduction mammoplasty in patients with personal history of breast cancer

Patients with a history of breast cancer usually undergo a close surveillance by mammography, ultrasonography and MRI. Despite the close monitoring, the incidence of APL still remains relatively high in risk reducing mammoplasty in those patients [15]. In our recent study, the frequency of APLs in patients with personal history of breast cancer is significantly high (12.8%) [16].

“Additionally, patients with previous breast reduction have been found to have low mortality from breast cancer compared with the general population.”

The age has been identified to be an important determining factor and significantly correlated with the incidence of APLs in this cohort. Patients >50 years had a 19.8% incidence of APL compared with 6.7% in patients <50 years (p < 0.05) [16].

Significance and challenges of finding APL in reduction mammoplasty

The presence of APL in reduction mammoplasty may be significant and challenging in patient management decisions. These challenges are mainly due to nonorientation of the reduction specimens with consequent improper evaluation of the margin status in some cases [17]. One of the options to deal with cases with undetermined margin status is to excise additional mass (lumpectomy) [7]. However, others recommended completion mastectomy with or without sentinel lymph node biopsy [15,17]. Irrespective of the approach, the question of ‘To what extent is important to find out if there is an occult carcinoma in these specimens’ exists. As reported, most of these occult carcinomas are low-grade (Gl), small (Tl), hormone- (ER and PR) positive tumors with favorable outcome [16].

In comparison to age-matched women, those with breast reduction for macromastia were found to have subsequent lower frequency of breast cancer [18–24]. It appears to be no difference in the risk reduction in premenopausal or postmenopausal women with previous breast reduction [19]. The reduced risk appears also not to be different in women with mutation in BRCA1 or BRCA2 genes or with family history of breast cancer [19–20,23]. The reported risk reduction in patients with previous reduction mammoplasty has been estimated to be from 30 to 90% compared with those with no such surgery [18,21,24].

The reduced risk could be explained by undocumented (missed) cancers in a fraction of the reduction specimens or may be due to a protective effect by removing the excess breast parenchyma in which the cancers may develop. At minimum, reduction mammoplasty is protective or at least did not have poor outcome [18–24]. For how long after surgery the woman has reduced risk of breast cancer differs according to the follow-up interval after the surgery. A number of studies [24,25] reported protection for only 10 years post-reduction. However, the mean follow-up period in these two studies was 10 years and it is possible that the short-term protective effect of reduction mammoplasty may be due to the short-term follow-up itself. In one study [21] with longer follow-up (mean of 16 years), the reduced risk of breast cancer among those with previous reduction mammoplasty has been estimated to be 30%. Additionally, in the same study, a similar (30%) reduction in breast cancer mortality was also found for women who underwent reduction mammoplasty. Interestingly, the protective effect of reduction mammoplasty extends to all age groups in that study with large cohort of 30,444 cases [21].

It has been reported that women with morbid macromastia may be suffering from social and/or psychological challenges especially in accepting their body image [26,27]. In addition to the reported benefits of cancer and mortality risk reduction in patients who underwent reduction mammoplasty, patients may have social and emotional benefits including high self-confidence and acceptance of body image after the surgery [28,29]. Reduction mammoplasty was found to improve pain symptoms, for example, shoulder, upper/lower back, neck, breast, headache and pain/numbness in the hands compared with the pre-reduction status. The quality-of-life of physical functioning was also improved ([30] and references therein).

It is obvious that identifying an invasive carcinoma or DCIS in reduction specimens has clinical implications. The issue of identifying other APLs such as lobular carcinoma in situ, atypical ductal hyperplasia and flat epithelial atypia is controversial [8]. It is important to identify APLs in patients especially those with no personal history of breast cancer. This would give the opportunity to intervene with increased surveillance and risk reduction strategies in order to early detect a future breast cancer and in order to reduce the risk for subsequent breast cancer development. For patients with personal history of breast cancer, the above interventions are probably in place already which may minimize the clinical significance of additional incidental APLs.

In conclusion, the frequency of detection of APL in patients with no history of breast cancer is significantly low (4.3%) compared with 12.8% in those with history of breast cancer. Among APLs, the incidence of invasive carcinoma and DCIS is extraordinarily low at 0.2%. Age has been identified to be a contributing factor in identifying APL with more detection in advanced age. Breast reduction performed mainly for macromastia has been found to be beneficial physically as a breast cancer risk reducing procedure and psychologically by improving quality of life and pre-reduction pain symptoms. Additionally, patients with previous breast reduction have been found to have low mortality from breast cancer compared with the general population.