INTRODUCTION:

Due to hormonal stimulation, pregnancy and breastfeeding reflect typical physiological changes in the breast tissue. The majority of benign breast lesions discovered during pregnancy. Up to 3% of all breast malignancies are pregnancy-associated breast cancers (PABC) ¹. In affluent nations, the prevalence of PABC among pregnancies is believed to be between 1/10,000 and 1/3000, and it may represent up to 6.25% of all breast cancers discovered in fertile women under the age of 45 ^2,3,4.

A woman's risk for breast cancer may increase by double if a first-degree relative has the illness. BRCA1 and BRCA2 gene mutations predispose carriers to the illness⁵.

According to research, breast cancer is the second most frequent kind of cancer during pregnancy. The age range is between 32 and 38 years. As women age and breast cancer rates continue to climb, more cases of PABC are expected to be diagnosed⁶. Given that physiological changes during pregnancy might delay diagnosis and treatment, detecting cancer during pregnancy can be difficult⁷. Breast lesions may be seen with ultrasound, mammography, and MRI with contrast. The majority of benign breast lumps may be found with ultrasound, which is the first line modality since it is non-ionizing radiation and safe. Studies have shown that it has a great sensitivity for identifying PABC, with 100% sensitivity and 100% negative predictive value. With the right protection, mammography is typically safe during pregnancy and breastfeeding⁸. It is thought that exposure to more than 0.05 Gy of radiation during the first trimester results in foetal abnormalities. With abdominal shielding, standard two-view mammography of each breast exposes the foetus to just 0.004 Gy of radiation⁹. Mammography has a detection sensitivity of 78% to 90% for PABC. The increased parynchymal density brought on by pregnancy hormones may be the source of this decreased sensitivity¹⁰.

Although MRI involves no irradiation, there are limitations for its use in the diagnosis of breast cancer in pregnant and lactating women. Gadolinium crosses the placenta, and is associated with fetal abnormalities¹¹.

Biopsy should be performed to obtain a pathologic diagnosis when the imaging results are suspicious and for grading of malignancy⁹.

Fine-needle aspiration (FNA) during pregnancy may be associated with increased false-positive as well as increased false-negative rates. Ultrasound guided core biopsy is cost-effective and the standard procedure for assessing breast masses during pregnancy and lactation. Comploications of core biopsy include increased risk of bleeding, milk fistula formation and infection. These risks can be minimized by stopping breastfeeding before the biopsy, proper haemostasis and strict asepsis¹².

A wide variety of breast lesions may be encountered during pregnancy and lactation. The most common problems are lactational change/lobular hyperplasia, lactational adenoma and lactational calcifications. The following benign lesions can also be encountered: galactocele, fibroadenoma, obstructed milk duct, mastitis with or without abscess, granulomatous mastitis, hyperplastic intramammary and/or axillary lymph nodes. Malignant lesions include PABC and metastatic disease¹³.

PABC typically present as a painless palpable lump. Diagnosis is sometimes delayed as physical examination of the pregnant and lactating breast is challenging. Overall, PABC is biologically aggressive and has a poorer prognosis, as the majority of these tumors are estrogen and progesterone receptor negative and Her2-neu receptor positive¹³.

Therefore, obstetricians should be aware that a thorough evaluation of any lesion is mandatory, to help detect malignancy in its early stage¹⁴.

Aim of the work:

Our aim is to diagnose breast lesions during pregnancy and lactation among patients attending Kasr Al Ainy

Patients and methods:

500 pregnant and lactating patients attending Kasr Al Ainy outpatient clinic from the period between 3/2018 to 12/2019 having breast complaints were included in the study. An informed consent was obtained from all patients. Ethical approval was obtained from Cairo University committee.

Thorough breast examination was performed for all patients. Inspection and palpation of the breast was performed, to confirm the presence of a mass, to identify its location and size, to describe consistency and mobility and to detect related signs as skin retraction, nipple discharge/changes, lymph node enlargement or signs of inflammation.

All patientswere subjected to breast ultrasound. Breast Imaging-Reporting and Data System (BIRADS) 1 and 2 will have no further investigations. BIRADS 3 will have a 6 month follow up. BIRADS 4 and 5 will have one of the following investigations: mammography, MRI with contrast or core biopsy according to the indication. Pathological examination was conducted at the pathology department, Cairo University.

Statistical analysis:

Data were coded andentered using the statistical package for the social sciences (SPSS) version 25 (IBM Crop., Armonk, NY, USA). Data was summarized using mean, standard deviation, median, minimum and maximum in quantitative data and using frequency (count) and relative frequency (percentage) for categoral data.

RESULTS:

Age of patients ranged between 18-40years.Of the 500 patients, 444 were pregnant (190 primigravida, 254 multigravida) and 56 were lactating. Gestational age ranged between 10-38 weeks in pregnant women (Table 1).

Breast mass was the commonest complaint (64.2%) followed by breast pain (47%). Other complaints were nipple discharge (5.6%) and fever (3%) (Table 2).

An actual breast mass by clinical examination was detected in 128 cases (25.6%), of which 104 cases (81.25%) were pregnant and 24 were lactating (18.75%). 5 cases had bilateral masses (3.9%).

The mass size ranged between 3 and 9cm (mean 5.6cm). The mass was firm in 124 cases (96.8%) and hard in 4 cases (3.1%), was mobile in 108 cases (84.3%) and had limited mobility in 20 cases (15.6%) (Table 3).

Skin changes were detected in 29/500 patients (2 skin edema, 1 bluish skin, 1 peaud’orange, 2 breast scars and 23 skin redness).

Nipple changes were found in 31/500cases (3 polythelia, 6 retracted nipples and 22 nipple erosion).

Ultrasound was performed for all patients. Ultrasound of 128 patients who had a mass during examination showed the following results: 93 fibroadenoma (72.6%), 10 duct papilloma (7.81%), 8 breast abscess (6.25%), 6 lactating adenoma (4.6%), 2 galactocele (1.56%), 2 granulomatous mastitis (1.56%), 5 suspicious masses (3.9%), 1 suspicious microcalcifications (0.78%), 1 inflammatory carcinoma (0.78%) (Table 4).

Thirteencases were referred to mammography and 2 were referred to MRI (all were lactating). Eightcases underwent abscess aspiration for culture and sensitivity.

Mammography results (all lactating) showed 4 normal lactational changes, 4 lactational mastitis, 1 galactocele, 2 granulomatous mastitis and 2 suspicious breast lesions.MRI results (all lactating) showed 2 suspicious breast masses.

Core biopsy was performed for 13 cases,4 were lactating and 9 were pregnant.7 cases were confirmed PABC (4 lactating, 3 pregnant) (Table 5).

Incidence of PABC was 5.46% (7/128) in patients with breast mass and 1.4% of all patients (7/500).

Pathological diagnosis of core biopsy ¹³ included 7 malignant cases (5 invasive duct carcinoma, 1 inflammatory carcinoma, 1 adenocarcinoma), 2 granulomatous mastitis and 4 fibroadenomas (Table 6).

Family history was positive in 6 of the 7 malignant cases (85.7%).

Cases with malignancy complained of mass(3/7), pain(1/7) or both(3/7). By examination, all had a hard mass with limited mobility, 2 patients had skin changes, 2 had retracted nipple,3 had positive axillary lymph nodes.

Ultrasound of malignant cases ranged from BIRADS 4a to 5 (Table 7).

Table 1 Demographic data:

	Mean +/- SD	Median
Age (years)	29.5+/- 5.27	30
GA (Weeks)	28.37+/- 6.02	29

Table 2: Patient’s complaints:

	Number	%
Breast mass	321	64.2%
Breast pain	235	47%
Nipple discharge	28	5.6%
Fever	15	3%

Table 3: Clinical assessment of breast mass (128):

		Number (%)
Mass	yes	128 (25.6%)
Mass	no	372 (74.4%)
Location of mass	Rt	63 (49.2%)
	Lt	60 (46.8%)
	bilateral	5 (4%)
Size	3cm	36 (28.1%)
	4cm	47 (37.3%)
	5cm	24
	6cm	15
	7cm	4
	9cm	2
Consistancy	Firm	124
Consistancy	Hard	4
Mobility	Mobile	108
Mobility	Limited mobility	20

Table 4: Ultrasound results:

Ultrasound finding	Number (%)
Fibroadenoma	93 (72.6%)
Duct papilloma	10 (7.8%)
Lactating adenoma	6 (4.68%)
Breast abscess	8 (6.25%)
Galactocele	2 (1.56%)
Granulomatous mastitis	2 (1.56%)
Suspicious Breast mass	5 (3.9%)
Suspicious calcifications	1 (0.78%)
Inflammatory carcinoma	1 (0.78%))

Table 5: Investigations of breast lesions:

	Lesion	Number (%)
Mammography (all lactating)	Suspicious	2 (0.4%)
	Granulomatous mastitis	2 (0.4%)
	Galactocele	1(0.2%)
	Lactational mastitis	4 (0.8%)
	Normal lactational findings	4 (0.8%)
Biopsy (pregnant and lactating)	True cut biopsy	12 (2.4%)
Biopsy (pregnant and lactating)	Excision during CS	1 (0.2%)
Aspiration for culture and sensitivity (lactating)	yes	8 (1.6%)
MRI (all lactating)	yes	2 (0.4%)

Table 6: Pathological results of core biopsy (13 cases):

Pathology	Number (%)
Invasive duct Ca	5 (38.4%)
Inflammatory Ca	1 (7.6%)
Undifferentiated adeno Ca	1 (7.6%)
Granulomatous mastitis	2 (16.9%)
Fibroadenoma	4 (30.7%)

Table 7: Data of malignant cases:

	Age	Gravida	Pregnant/ lactating	Family history	C/O	Examination	Ultrasound	Core Biopsy
1	35	multi	Pregnant 30weeks	+ve	Mass	Hard mass, 3cm, limited mobility	US BIRADS 5	Invasive duct CA
2	38	multi	lactating	-ve	Mass	Hard mass, 4 cm, limited mobility, nipple retraction, skin edema	US and mammography BIRADS 5	Invasive duct CA
3	35	primi	lactating	+ve	pain	Ill-defined nodular mass, 3cm, Axillary nodes +ve	US BIRADS 4, MRI Axillary nodes 1.3 cm,	Invasive duct CA
4	40	multi	lactating	+ve	Pain, mass	Ill-defined hard mass,3 cm, limited mobility	US and mammograph, BIRADS 4 MRI	Invasive duct CA
5	33	primi	lactating	+ve	Pain, mass	Ill-defined mass, 2 cm, hard, limited mobility, +ve LNs	US, mammograph: BIRADS4c/5	Invasive duct CA
6	26	multi	Pregnant 34 weeks	-ve	Pain, mass	Hard mass, 4 cm, limited mobility, Peaud’orangeslin, retracted nipple	US: BIRADS 4a	Inflammatory CA
7	41	multi	Pregnant 28 weeks	+ve	mass	Mass 4cm, hard, limited mobility, +ve LNs	US: BIRADS 4b	Undifferentiated Adeno CA

DISCUSSION:

A woman's breasts go through a number of physiological changes because of hormonal changes throughout pregnancy and nursing. Vascular hyperplasia and hyperplastic lobules may occur from this ¹. The interpretation of physical examination and medical imaging data may be hampered by such alterations. It should be highlighted that the majority of breast lesions identified during pregnancy and breastfeeding are benign, and that breast cancer detection is difficult during these times ¹⁵.

In order to identify breast lesions during pregnancy and breastfeeding, find the prevalence of breast masses, and find the prevalence and early diagnosis of PABC, we did this research. We included 500 ob/gyn outpatient clinic patients from Kasr Alainy hospital, Cairo University, who were pregnant or nursing and had breast symptoms.

Patients with PABC (7 instances) in our research varied in age from 26 to 41. They were 35 years old on average. This was in line with Rovera and colleagues' findings, who studied 12 patients with PABC and found that the median age was 34 years (range, 28 to 44). ¹⁶. Wang et al discovered that the median age at diagnosis was 30 years ¹⁷. Age ranged from 19 to 39 (mean 29) in a study by Hosny et al. that included 48 Egyptian patients with PABC ⁹.

Genetic testing need to be made available to all breast cancer patients under the age of 40. Pregnancy increases the risk of oestrogen receptor negative breast cancer, however this rise may be unnatural since high amounts of circulating oestrogen interfere with the binding test ¹⁸.

Pregnant women who had breast cancer before the age of 40 and were BRCA1 and BRCA2 carriers had a higher risk of developing the disease. High levels of circulating estrogens during pregnancy in women with the BRCA mutation might hasten a preexisting malignant transformation ¹⁹. Cancers that are discovered earlier in life tend to be more aggressive than those that are discovered later in life. Because of this, women who develop breast cancer during pregnancy often do so more aggressively and at a more advanced stage ²⁰.

In our research, lactating patients had a higher rate of PABC than pregnant ones. Nearly two-thirds of all PABC cases, often in the first six months after birth, were detected in the postpartum period, according to Smith et al. (2003) and Ives et al. (2005) ³^,⁴. According to a different research, PABC is much lower during pregnancy (between 3.0 and 7.7/100,000) than it is during the postpartum period (13.8 to 32.2/100,000). ^21,22.

In our research, breast discomfort was the most often reported ailment (47%), followed by breast bulk (64.5%). By ultrasound and physical examination, only 25.6% of women had a breast mass. In our investigation, every instance of malignancy had a breast lump upon presentation. Similar findings were made by Wang et al. in 2019 who discovered that all PABC patients had a palpable breast lump ¹⁷. All patients had a breast mass, according to Lamiaa et al2019 .'s research (23,24). According to two studies, 90.5% of women with PABC had a palpable mass. Given that just two of the studies included self-reported palpable masses, and given that other masses may have been discovered after a professional examination, this high percentage may even be underestimated ²³^,²¹. According to Theriault's research from 2007, the majority of women with PABC appear with either a painless lump in the breast or thickening of the breast skin ²⁴.

In our research, the total incidence of PABC was 1.4% (7/500). According to a research done in India, the prevalence of PABC was 0.6% nationwide ²⁵. In a survey of women from Romania, the prevalence of PABC was 4.4%. ²⁶. Another research discovered that 142 (0.36%) of the 40 000 breast cancer patients in Tianjin had PABC ¹⁷. The variation in incidence may be related to the number of patients analysed, the postpartum period's inclusion criteria, and the racial differences.

Patients with a breast mass had an incidence of 5.46%, according to our research. Hosny et al. (2011) also discovered that this incidence was 6.25%. ⁹. According to Lamiaa et al., 2019 it was 15%. ²².

In our investigation, the mass sizes varied from 3 to 9 cm. The bulk size in PABC was 2-4 cm (median 3cm). By examination and imaging, 3 instances (42.8%) revealed lymph nodes that were positive. According to Wang et al., 2019, axillary lymph node metastases were seen in 63.1% of patients, and the median tumour size was 5.5 cm ¹⁷.

In our analysis, undifferentiated adenocarcinoma (14.2%), inflammatory carcinoma (14.2%), and invasive duct carcinoma (5/7, 71.4%) were the most frequent pathology diagnoses. Invasive duct carcinoma was the most prevalent histologic type of PABC, making up 91.5% (130/142), according to Wang et al., 2019. This was followed by medullary carcinoma (n = 4), invasive lobular carcinoma (n = 3), mixed mucinous carcinoma (n = 1), tubular carcinoma (n = 1), and squamous cell carcinoma (n = 1). (17). This incidence was determined to be 100% by Lamiaa et al ²².

30% of patients had first-degree positive family histories, according to our research. In patients with PABC, this incidence was 85.7%. In a 2013 research by Chandnani et al., who examined breast masses in non-pregnant women, they discovered that patients with cancer had a family history in 27.5% of cases, compared to 14% of patients with benign breast masses ¹⁴. Patients with breast cancer during pregnancy or breastfeeding were three times more likely to have a favorable family history than other breast cancer patients in a Japanese case-control study ²⁷. Others didn't agree with this ²⁸. The variation in those figures may be explained by the variation in the number of patients evaluated, the variation in ethnicity, and the degree of family involvement ^29-36.

CONCLUSION:

We found he majority of breast masses during pregnancy and lactation to be benign. Incidence of PABC was overall 1.4% and 5.46%in patients who were diagnosed with a breast mass. Ultrasound constitutes the most appropriate radiologic method for evaluating breast disorders in women during pregnancy and lactation. Biopsy is mandatory for suspicious cases. Obstetricians should be aware that a thorough evaluation of any lesion is mandatory, to rule out malignancy.

THERE WAS NO CONFLICT OF INTEREST:

The study was not funded

ACKNOWLEDGEMENT:

We would like to thank the pathology department, Kasr Al Ainy, Cairo University.

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Received on 14.08.2022 Modified on 17.10.2022

Research J. Pharm. and Tech 2023; 16(4):1679-1684.

DOI: 10.52711/0974-360X.2023.00275