Mastalgia, nipple discharge, and palpable breast masses are commonly encountered in outpatient settings. The first step is to start with a detailed clinical history and physical examination. Diagnostic mammography is generally preferred; however, ultrasonography is more sensitive in women under 30 years of age. In cases of suspicious masses detected during physical examination, mammography, or ultrasonography, a biopsy should be performed. Mastalgia is rarely an indicator of underlying malignancy. Oral contraceptives, hormone therapy, certain psychotropic drugs, and cardiovascular agents can cause mastalgia.
In the diagnostic evaluation of patients with nipple discharge, the first step is to classify the discharge as pathological or physiological. Nipple discharge is classified as pathological if it is spontaneous, bloody, unilateral, or associated with a breast mass. Diagnostic imaging should be performed in patients with pathological nipple discharge. If nipple discharge is bilateral, originates from multiple ducts, and occurs with squeezing, it is usually physiological. In patients with physiological discharge, systemic causes of nipple discharge (such as hyperprolactinemia or thyroid dysfunction) should be ruled out by measuring thyroid-stimulating hormone (TSH) and prolactin (PRL) levels, and the use of dopamine-inhibiting drugs should be investigated. Treatment of nipple discharge depends on the etiology. Physiological discharge often resolves spontaneously without any treatment; however, if nipple discharge is due to systemic causes, medical treatment may be necessary.
Nipple Discharge
Approximately 80% of women experience nipple discharge at some point in their lives(1). The key is to differentiate between pathological and physiological discharge and to avoid missing a cancer diagnosis. In patients presenting with nipple discharge, the onset of discharge, its relationship with the menstrual cycle, age at first pregnancy, birth history, age of menarche and menopause, laterality (unilateral or bilateral), whether it is spontaneous or induced, persistent or intermittent, and its consistency and color should be questioned.
A history of breast complaints, breast biopsy, breast surgery, trauma, hysterectomy or oophorectomy, breastfeeding, oral contraceptive (OC) use, hormone replacement, and other drug usage should be investigated. Associated fever may indicate mastitis or breast abscess; weight gain, cold intolerance, amenorrhea may point to hypothyroidism; ascites and jaundice may suggest liver disease; visual disturbances, headache, and amenorrhea may indicate a pituitary tumor(2). Types of discharge:
Lactational: Occurs during pregnancy, postpartum period, or with prolactinomas.
Physiological: The most common type of discharge. It can be white, green, yellow, gray, or brown in color. It is usually bilateral, originates from multiple ducts, and occurs with squeezing. It may be due to hypothyroidism, medication use (dopamine inhibitors), hormonal causes, or fibrocystic disease.
Pathological: Generally spontaneous, originates from a single duct, and is unilateral. The color may be clear, serous, or bloody. The presence of an accompanying mass should be investigated during physical examination. It is often caused by intraductal papilloma. Underlying ductal ectasia, cancer, periductal mastitis, or abscess should also be considered.
Nipple discharge is very common, representing the third most frequent breast complaint after pain and masses, with a prevalence of 5-10%. Underlying breast cancer is seen in 7-15% of cases with pathological nipple discharge (3, 4). Particular caution should be exercised in women with BRCA 1 and 2 mutations, a history of ipsilateral breast cancer or atypia, a family history of breast or ovarian cancer, and women over 40 or in the postmenopausal period presenting with nipple discharge. During physical examination, the nipple, areola, and discharge color should be examined with magnification and light for focused inspection. Attention should be given to the presence of palpable masses and the position of the nipple. In pathological discharge, masses, swelling, redness, skin retraction, or nipple retraction may occur. The origin of the discharge ducts is investigated using a pressure point exam(2).
The sensitivity of screening mammography (MMG) depends on breast density, but it is generally performed in women over 40 years of age or in the presence of suspicious ultrasonographic (US) findings in women under 40 years of age (5). It is particularly useful for detecting microcalcifications, masses, focal density asymmetry, structural distortions, or ductal ectasia. In cases of ductal ectasia, spot compression imaging may be necessary. Sensitivity for small retroareolar or intraductal lesions is low. On magnification MMG, round or tubular microcalcifications are likely benign, while branched, linear, segmentally distributed, and variably dense microcalcifications are more likely malignant. The presence of a single dilated duct on MMG may indicate an intraductal papilloma or carcinoma. Targeted breast US, magnetic resonance imaging (MRI), or galactography may be performed. If no correlation is established, duct excision is necessary.
Ultrasonography better demonstrates intraductal lesions, particularly in dense breasts, with sensitivity ranging from 63-100% and specificity from 73-84%. Ductal ectasia appears as ducts larger than 2mm in diameter or 3mm in the ampullary portion, containing anechoic fluid or hypoechoic debris (6). Intraductal papilloma appears as a hypoechoic nodule with a central vascular pedicle on Doppler US. In the presence of cancer, irregular ductal margins, wall thickening, and intraductal masses with acoustic shadowing may be seen. Although elastography has high sensitivity for malignancies, data on this method are limited (7).
Cytological examination of the discharge is not routinely recommended due to low sensitivity for detecting cancer and high rates of false negatives (1). It is technically challenging when discharge is not present. Papillary, atypical, suspicious, or malignant cells are diagnostic. Galactography (ductography) is invasive, painful, and technically challenging, with high false-negative rates and positive predictive value of 19%, and negative predictive value of 63%. It is insufficient for differentiating underlying pathology and ruling out malignancy (8). Ductoscopy, using 0.45-1.2mm microendoscopes with a 0.2mm injection channel, allows direct visualization and guided surgical excision, with examination up to an average depth of 5-6cm. It is performed under local anesthesia. Interventional procedures include ductal lavage, ductal cytology, intraductal vacuum biopsy, biopsy with endoluminal brushes and forceps, and papilloma removal with endobaskets. It preserves healthy tissue and ducts. While major ducts and branches can be examined via direct intraductal visualization, deeper and minor branches may not be seen. It cannot be performed in cases of inverted nipples, narrow ducts, obstructive lesions, or pain.
Contrast-enhanced magnetic resonance imaging (MRI) has sensitivity exceeding 90% for breast cancer, making it highly effective (9). Cancer exhibits segmental, linear, or non-mass-like enhancement; papillomas appear as well-defined homogenous masses; ductal dilatation shows increased signal intensity. It provides diagnostic advantages for multifocal or multicentric disease detection, evaluation of the contralateral breast, physiological evaluation, intermittent suspicious discharge, or discharge originating from multiple ducts. It is recommended for evaluating the etiology of nipple discharge not visualized with conventional methods. Targeted US is suggested for suspicious lesions identified on MRI.
Diagnosis of high-risk lesions can be made using MMG and US; MRI and ductography can be used as needed. If these methods fail to provide a diagnosis, surgical excision is performed. Galactography combined with tomosynthesis provides results similar to MRI and ductal sonography but has disadvantages such as ductal cannulation, contrast agent injection, and radiation exposure.
In low-risk patients with physiological nipple discharge and normal clinical and radiological findings, follow-up with examinations and US every six months and annual MMG is recommended. Most cases resolve spontaneously. If discharge persists, ductoscopy, ductography, or MRI may be performed. Ductoscopy-guided excision, wire or methylene blue localization for lesions deeper than 1.5-2cm, central duct excision for lesions near the nipple, microductectomy under lacrimal probe guidance, and percutaneous vacuum biopsy under US guidance may be performed. Central duct excision is applied for bilateral, multichannel, green, or milk-colored benign nipple discharge with significant patient complaints or clinical and radiological suspicion. However, hormonal and drug etiology should be excluded.
In cases of a personal or family history of breast cancer, palliative treatment intent, or when patients do not desire follow-up, surgery may be performed. Risk stratification and follow-up significantly prevent unnecessary surgeries. In high-risk patients, new-onset discharge or new mammographic asymmetry warrants biopsy or subareolar excision (major duct excision, microductectomy) under imaging guidance. Total subareolar duct excision (central duct excision) has a high rate of detecting occult cancers. For younger and breastfeeding candidates, selective duct excision (microductectomy) is recommended (10).
In summary, for physiological nipple discharge without palpable masses, clinical follow-up with MMG for patients over 40 years and US for those under 40 years is recommended. For pathological nipple discharge, ductogram or MRI is advised in cases of normal imaging, and duct excision is recommended if necessary. In cases of abnormal imaging, biopsy is performed, and if benign/indeterminate pathology is reported, ductogram or MRI followed by duct excision is advised if necessary (1).
Mastalgia
Mastalgia is common in women, with 70% of the female population experiencing breast pain at some point in their lives. While the pain is often mild and self-limiting, approximately 15% of patients require treatment. The cause of mastalgia should be distinguished as being due to physiological changes from hormonal fluctuations or resulting from pathological processes such as cancer or
inflammation. A study involving 1,659 women found that 51.5% experienced breast pain. Older age, macromastia, higher body weight, and lower physical activity were associated with more frequent complaints of breast pain. Nearly 40% of symptomatic patients reported that mastalgia negatively impacted their quality of life, including sexual health and sleep patterns (11).
Mastalgia can be cyclical, non-cyclical, or extramammary in origin. Cyclical breast pain accounts for two-thirds of mastalgia cases and is associated with hormonal fluctuations. It begins in the week before menstruation, is bilateral, localized to the upper outer quadrants, and resolves with the onset of menstruation. Fibrocystic changes may also cause cyclical breast pain (12). Non-cyclical breast pain accounts for one-third of mastalgia cases. It does not follow a cycle. It is constant or intermittent, more often unilateral, and variable in localization. Breast and chest wall lesions are more likely. It can be observed in pendulous (sagging) breasts. Neck, back, and shoulder pain may accompany. It has been associated with fatty diets, smoking, and caffeine intake, although there is no high-quality evidence to support this. Postmenopausal hormone therapy or OC use can cause mastalgia that resolves spontaneously (13, 14). Extramammary pain can result from intercostal neuralgia (at T3-5 levels), gallbladder or esophageal pathologies, cardiac causes, chest wall pathologies (pectoralis muscle injury, costochondritis between the 2nd-5th ribs), spinal and paraspinal muscle issues, or trauma.
Imaging with MMG and breast US can be performed in the presence of mastalgia. The rate of breast cancer detection on MMG in patients examined for breast pain is not higher than in those without pain. Breast cancer is detected in 0-4% of patients undergoing US for breast pain without palpable masses, and only half of the cancers detected are located in the area of pain (15, 16). Imaging is generally unnecessary for cyclical and bilateral diffuse mastalgia. For non-cyclical, unilateral, focal breast pain, imaging is recommended based on age to clarify the etiology and rule out cancer. US is recommended for those under 30; MMG for those aged 30-39 with suspicious US findings; MMG and US for those over 40.
If clinical and imaging findings are normal, providing reassurance to the patient is sufficient. Knowing that they do not have cancer provides 78-85% of patients with relief. If quality of life is impaired, treatment is necessary. Approximately 15% of patients with mastalgia require treatment. Surgery is not indicated in the absence of breast pathology (17, 18). First-line treatments include reassurance of the absence of malignancy, physical support, analgesics, hormone-based medication adjustments, and caffeine restriction. Physical support involves tight clothing, well-fitting bras, padding the other side in cases of asymmetry, hot compresses, ice packs, and massage. Medical treatment includes acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs). Topical NSAIDs such as salicylate, ibuprofen, and diclofenac can also be used (19). These treatments should be tried for six months before moving to second-line therapies. For resistant cases, second-line treatment includes tamoxifen at 10-20mg/day for three months. Side effects of tamoxifen include hot flashes, vaginal dryness, joint pain, blood clotting, uterine cancer, cataracts, and cerebrovascular events. Danazol (androgen) can be started at 200mg/day. It has been shown to reduce pain by 20% on the Visual Analog Scale (VAS). However, side effects include weight gain, menstrual irregularities, voice deepening, and hot flashes. Tamoxifen and danazol side effects can be reduced by using them during the luteal phase of menstruation (20).
For women on hormones, postmenopausal hormone use should be reduced if possible. Estrogen doses in OCs can be lowered. Some studies suggest that OCs reduce mastalgia, but this may vary depending on the OC composition. Progesterone can alleviate mastalgia in some women. Randomized studies have not shown effects of oral and topical progesterone, but vaginal creams (micronized progesterone) have been found to reduce mastalgia by 65%. Lifestyle changes, caffeine restriction, low-fat diets, and evening primrose oil are unproven treatments based on randomized trials. Vitamin E and bromocriptine have not shown significant effects in mastalgia treatment. Genistein, soy milk, agnus castus fruit extract, and chamomile extract are among the therapies being researched (22). For chest wall pain, acetaminophen, NSAIDs, local heat applications, local anesthetics, and corticosteroid trigger point injections may be used. Activities that exacerbate pain should be restricted (23). Mastalgia shows a 40% improvement with placebo treatment. Spontaneous improvement is observed in 20-50% of cases, with remissions and recurrences. Improvement may occur spontaneously or be related to pregnancy, menopause, or hormone mediation. It can also be treated as a component of the associated pathology. Premenstrual syndrome causes tenderness in the second half of menstruation, which is bilateral and diffuse. The use of selective serotonin reuptake inhibitors (SSRIs) may be effective in such patients (24).
