Search

Human milk extraction from the breast is affected by the infant's oral activities. Natural suckling by the infant includes both intraoral vacuum and peripheral oral compression during breastfeeding. However, the contribution of each of these motions to milk extraction at the outlet and at the duct bifurcations is unclear. In this work, we investigated the flow field in a lactating breast model considering bifurcated milk ducts and multiphase breast-infant interactions. A bio-inspired breastfeeding simulator device was utilized to mimic an infant's oral feeding mechanism during breastfeeding and extract the human milk-mimicking Fluid from the transparent and elastic lactating breast phantom during experiments. Using a particle image velocimetry system, we found that the oscillatory flow under vacuum pressure provides a higher velocity field at the outlet compared to that when an infant applies both vacuum and oral compression pressures. Additionally, the intraoral vacuum coordinated with the oral peripheral compression causes stronger vorticities and secondary flows at the adjunction of the bifurcated ducts than the vacuum-only case. Vacuum-only extraction yields an increase in flow velocity at the outlet and could be one of the reasons for nipple pain, whereas infant's oral activities on the breast generated more vortices in the milk duct adjunctions and might cause milk duct clogs. This phenomenon is rationalized based on the validation of a previous in vivo clinical study of milk production compared between commercial pumps and infant suckling. The fact that milk consumption of vacuum-only extraction is less than that of vacuum plus oral compression further explains the effectiveness of applying a natural suckling pattern in human lactation., (© 2021. Biomedical Engineering Society.)

Purpose of Review: The purpose of this review is to describe epidemiologic and toxicological literature investigating how endocrine-disrupting chemicals (EDCs) affect mammary gland development and function, thereby impacting lactation duration., Recent Findings: Perfluoroalkyl and polyfluoroalkyl substances appear to reduce breastfeeding duration through impaired mammary gland development, lactogenesis, and suppressed endocrine signaling. Halogenated aromatic hydrocarbons have differing associations with lactation duration, likely because of the variety of signaling pathways that they affect, pointing to the importance of complex mixtures in epidemiologic studies. Although epidemiologic literature suggests that pesticides and fungicides decrease or have no effect on lactation duration, toxicology literature suggests enhanced mammary gland development through estrogenic and/or antiandrogenic pathways. Toxicological studies suggest that phthalates may affect mammary gland development via estrogenic pathways but no association with lactation duration has been observed. Bisphenol A was associated with decreased duration of breastfeeding, likely through direct and indirect action on estrogenic pathways., Summary: EDCs play a role in mammary gland development, function, and lactogenesis, which can affect breastfeeding duration. Further research should explore direct mechanisms of EDCs on lactation, the significance of toxicant mixtures, and transgenerational effects of EDCs on lactation.

Childbirth at any age confers a transient increased risk for breast cancer in the first decade postpartum and this window of adverse effect extends over two decades in women with late-age first childbirth (>35 years of age). Crossover to the protective effect of pregnancy is dependent on age at first pregnancy, with young mothers receiving the most benefit. Furthermore, breast cancer diagnosis during the 5- to 10-year postpartum window associates with high risk for subsequent metastatic disease. Notably, lactation has been shown to be protective against breast cancer incidence overall, with varying degrees of protection by race, multiparity, and lifetime duration of lactation. An effect for lactation on breast cancer outcome after diagnosis has not been described. We discuss the most recent data and mechanistic insights underlying these epidemiologic findings. Postpartum involution of the breast has been identified as a key mediator of the increased risk for metastasis in women diagnosed within 5-10 years of a completed pregnancy. During breast involution, immune avoidance, increased lymphatic network, extracellular matrix remodeling, and increased seeding to the liver and lymph node work as interconnected pathways, leading to the adverse effect of a postpartum diagnosis. We al discuss a novel mechanism underlying the protective effect of breastfeeding. Collectively, these mechanistic insights offer potential therapeutic avenues for the prevention and/or improved treatment of postpartum breast cancer., (©2020 American Association for Cancer Research.)

Physical exam of the breast is a very important part of breast assessment both for breast cancer screening, and when approaching breast lesions. Examination during pregnancy and breastfeeding follows exactly the same method as non-pregnancy periods. However, physical changes that occur in the breast during these times due to hormonal effects cause alterations that can on one hand conceal some pathologic disorders, and may on the other hand appear as pathologic findings while being purely physiologic. This chapter focuses first on some key points for an accurate breast examination, and then reviews some challenging controversial findings that may be noticed during breast exam in a pregnant or lactating woman.

The mature breast is located within the anterior thoracic wall, lying atop the pectoralis major muscle. Pubertal changes lead to incomplete development of the breast , a process which is only completed during pregnancy . The incomplete breast consists mostly of adipose tissue but also lactiferous units called lobes. These eventually drain into the lactiferous ducts and then into the lactiferous sinus and then to the nipple-areolar complex. During pregnancy , the breast undergoes both anatomic and physiologic changes to prepare for lactation. During the first trimester, the ductal system expands and branches out into the adipose tissue in response to the increase of estrogen. Elevated levels of estrogen also cause a decrease in adipose tissue and ductal proliferation and elongation. Estrogen also stimulates the pituitary gland which leads to elevated levels of prolactin. By the twentieth week of gestation, mammary glands are sufficiently developed to produce components of milk due to prolactin stimulation. Milk production is inhibited by high estrogen and progesterone levels and colostrum is produced during this time. In the third trimester and then rapidly after birth, these levels decrease, allowing for milk production and eventual let-down to allow for breastfeeding. Most pregnancies cause the areola to darken, the breast to increase in size, and the Montgomery glands to become more prominent. Post-lactational involution occurs at the cessation of milk production caused by a decline in prolactin.

Objective: Knowledge on the hemodynamics of the human lactating breast contributes to our understanding of lactation physiology, as well as the development and management of breastfeeding problems. The objective of this pilot study was to investigate whether laser Doppler perfusion monitoring (LDPM) can be employed to measure physiological changes in mammary cutaneous perfusion during milk extraction., Approach: We evaluated mammary cutaneous perfusion with LDPM in nine lactating women during milk extraction in both the ipsilateral ('milk extracting') and contralateral ('passive') breast. Fourier domain filtering of the LDPM signal was applied to correct for the influence of the periodic tissue movement caused by the breast pump., Main Results: Cutaneous perfusion increased temporary during 23.7  ±  18.9 s by 18%-74% for all women who sensed their milk ejection reflex (n  =  6) in both the ipsilateral and contralateral breast. For those women who did not sense a milk ejection reflex (n  =  3), the changes in cutaneous perfusion were less outspoken (maximally 26%)., Significance: This pilot study provides new insights into mammary hemodynamics and demonstrates that LDPM is a promising method for the further investigation of physiological changes in mammary cutaneous perfusion during milk ejection. Objective feedback on the occurrence and progression of milk ejection can support lactation research in general, maternal breastfeeding confidence, and may be an early indicator for the development of breastfeeding problems.

Relatively few imaging and sensing technologies are employed to study human lactation physiology. In particular, human mammary development during pregnancy as well as mammary involution after lactation have been poorly described, despite their importance for breast cancer diagnosis and treatment during these phases. Our case study shows the potential of diffuse optical spectroscopic imaging (DOSI) to uniquely study the spatiotemporal changes in mammary tissue composition during the involution of the lactating breast toward its pre-pregnant state. At nine time intervals over a period of eight months after the cessation of breastfeeding, we reconstructed 2-D maps of mammary water content, lipid content, total hemoglobin (THb) concentration, oxygen saturation (StO2), and tissue optical scattering. Mammary lipid content in the nonareolar region showed a significant relative increase of 59%, whereas water content and THb concentration showed a significant relative decrease of 50% and 48%, respectively. Significant changes were also found in StO2 and tissue optical scattering. Our findings are consistent with the gradual replacement of fibroglandular tissue by adipose tissue and vascular regression during mammary involution. Moreover, our data provide unique insight into the dynamics of breast tissue composition and demonstrate the effectiveness of DOSI as a technique to study human lactation physiology.

Objectives: Successful breastfeeding, crucial for a child's development, depends on a woman's ability to initiate lactation, milk yield, and composition. Those traits differ among women, but the cause and physiological mechanisms responsible for this variation are not fully understood yet. Growing evidence shows that lactation and milk composition vary among women and depend on maternal traits. The aim of this study was to test whether breast volume and its changes during pregnancy are related to the nutritional quality of breastmilk and to breastfeeding dynamics., Material and Methods: Almost 93 pregnant women (mean age: 29.67 ± 3.65), participated in the longitudinal study. Breast measurement was performed at each pregnancy trimester using 3D scanning. Milk samples were collected in the beginning of the second month of lactation from 69 women. Milk macronutrient and calorie content were measured. Women were also interviewed on breastfeeding time and frequency., Results: Breast volume changes during pregnancy were not related to the probability of establishing successful lactation, milk calorie, fat and protein content. We found a negative correlation between milk lactose content and breast volume in the second and third trimester but not with breast volume change. Maternal breast volume in pregnancy was also positively related to the total breastfeeding time (per 24 hr)., Conclusions: The results are in line with the notion that milk macronutrient content tends to be weakly associated with various maternal factors and adverse conditions. However, maternal breast volume and its changes during pregnancy are related with time spent breastfeeding per day, what suggests a positive correlation between breast volume in pregnancy and milk yield., (© 2018 Wiley Periodicals, Inc.)

Breastmilk is the physiologic norm for infant nutrition. Despite recommendations from major health organizations, many women in the U.S. are not achieving this metric. Understanding breast anatomy and lactation physiology will allow physicians to gain knowledge of the processes, which control lactation enabling physicians to appropriately manage the breastfeeding dyad. The interplay of hormones involved in lactation and milk management affect milk initiation, as well as ongoing milk production (galactopoesis). The unique components of breastmilk that provide protection against infection and chronic diseases also change between and during feeds. Colostrum and the importance of early skin-to-skin after delivery will also be discussed., (Copyright © 2016 Mosby, Inc. All rights reserved.)

Lactation and the return to the pre-conception state during post-weaning are regulated by hormonal induced processes that modify the microstructure of the mammary gland, leading to changes in the features of the ductal / glandular tissue, the stroma and the fat tissue. These changes create a challenge in the radiological workup of breast disorder during lactation and early post-weaning. Here we present non-invasive MRI protocols designed to record in vivo high spatial resolution, T 2 -weighted images and diffusion tensor images of the entire mammary gland. Advanced imaging processing tools enabled tracking the changes in the anatomical and microstructural features of the mammary gland from the time of lactation to post-weaning. Specifically, by using diffusion tensor imaging (DTI) it was possible to quantitatively distinguish between the ductal / glandular tissue distention during lactation and the post-weaning involution. The application of the T 2 -weighted imaging and DTI is completely safe, non-invasive and uses intrinsic contrast based on differences in transverse relaxation rates and water diffusion rates in various directions, respectively. This study provides a basis for further in-vivo monitoring of changes during the mammary developmental stages, as well as identifying changes due to malignant transformation in patients with pregnancy associated breast cancer (PABC).

One of the important challenges in surrogate pregnancies is the early bonding of genetic mother with her infant and the establishment of breastfeeding. A combination of pharmacological and nonpharmacological methods is often used for the induction of lactation. Reports of induced lactation in surrogacy are limited and scattered. In this report, we present a case of induced lactation and initiation of breastfeeding in preterm twins by the genetic mother, through her novel approach after a gestational surrogate pregnancy. Thematic approach of maternal account is summarized with context and rigor. We reviewed the reported literature of induced lactation in similar cases with an aim to address the various methods adopted.

This study is a collaborative effort among lactation specialists and fluid dynamic engineers. The paper presents clinical results for suckling pressure pattern in lactating human breast as well as a 3D computational fluid dynamics (CFD) modeling of milk flow using these clinical inputs. The investigation starts with a careful, statistically representative measurement of suckling vacuum pressure, milk flow rate, and milk intake in a group of infants. The results from clinical data show that suckling action does not occur with constant suckling rate but changes in a rhythmic manner for infants. These pressure profiles are then used as the boundary condition for the CFD study using commercial ansys fluent software. For the geometric model of the ductal system of the human breast, this work takes advantage of a recent advance in the development of a validated phantom that has been produced as a ground truth for the imaging applications for the breast. The geometric model is introduced into CFD simulations with the aforementioned boundary conditions. The results for milk intake from the CFD simulation and clinical data were compared and cross validated. Also, the variation of milk intake versus suckling pressure are presented and analyzed. Both the clinical and CFD simulation show that the maximum milk flow rate is not related to the largest vacuum pressure or longest feeding duration indicating other factors influence the milk intake by infants.

Cleavage of adhesion proteins is the first step for physiological clearance of undesired cells during postlactational regression of the mammary gland, but also for cell migration in pathological states such as breast cancer. The intracellular Ca(2+)-dependent proteases, calpains (CAPNs), are known to cleave adhesion proteins. The isoform-specific function of CAPN1 and CAPN2 was explored and compared in two models of cell adhesion disruption: mice mammary gland during weaning-induced involution and breast cancer cell lines according to tumor subtype classification. In both models, E-cadherin, β-catenin, p-120, and talin-1 were cleaved as assessed by western blot analysis. Both CAPNs were able to cleave adhesion proteins from lactating mammary gland in vitro Nevertheless, CAPN2 was the only isoform found to co-localize with E-cadherin in cell junctions at the peak of lactation. CAPN2/E-cadherin in vivo interaction, analyzed by proximity ligation assay, was dramatically increased during involution. Calpain inhibitor administration prevented the cytosolic accumulation of truncated E-cadherin cleaved by CAPN2. Conversely, in breast cancer cells, CAPN2 was restricted to the nuclear compartment. The isoform-specific expression of CAPNs and CAPN activity was dependent on the breast cancer subtype. However, CAPN1 and CAPN2 knockdown cells showed that cleavage of adhesion proteins and cell migration was mediated by CAPN1, independently of the breast cancer cell line used. Data presented here suggest that the subcellular distribution of CAPN1 and CAPN2 is a major issue in target-substrate recognition; therefore, it determines the isoform-specific role of CAPNs during disruption of cell adhesion in either a physiological or a pathological context., (© 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.)

Background: The use of breast pumps with a compression component has shown their higher efficacy compared with vacuum pumps. However, the direct role of the compression stimulus is not sufficiently proven in the removal of milk from the main milk ducts of the breast. The aim of this study was to determine the contribution pulsating compression component of the breast pump has on total volume milk ejection by vacuum and compression stimuli., Subjects and Methods: Twenty-four lactating women of 21-30 years of age, who volunteered to be included in this study, were examined. Experimental breast pump with vacuum and compressive components were used to express breast milk., Results: It was found that volume milk ejection together with vacuum and compression stimuli was 10-46% more than expressing only with vacuum stimuli. Average values were 40.5% ± 5% for expression only with vacuum stimuli and 59.5% ± 5% for expression with vacuum and compression stimuli., Conclusions: Compression stimuli increased the efficacy of the breast pump, which is not only due to the effective formation milk ejection reflex but also directly to an additional squeezing of milk from the breast.

Introduction: Lactating breasts have greater uptake of fluorine-18 fluorodeoxyglucose (F-FDG) than nonlactating breasts; however, there are no published data on the radiation dose from F-FDG to lactating breasts or this effect on the effective dose (ED). In addition, the International Commission on Radiological Protection's (ICRP) most recently published ED of 1.9×10 mSv/MBq from F-FDG was calculated using weighting factors that have since been superseded. We therefore calculated the F-FDG radiation dose to the lactating breast, its effect on the ED and calculated more up-to-date EDs from F-FDG for nonlactating patients., Methods: Breast uptake of F-FDG and volume were determined from PET/CT images of a lactating patient. These data, together with previously published biokinetic data on F-FDG, were used to calculate a radiation dose to the lactating breasts and its effect on the ED. In addition, tissue weighting factors and organ doses from the ICRP publications 103 and 106 were used to calculate more up-to-date EDs from F-FDG in nonlactating patients., Results: The absorbed dose to the lactating breast from F-FDG is 1.75×10 mGy/MBq, which results in an increase in the ED of 6%. In nonlactating patients, a more up-to-date ED from F-FDG is 1.77×10 mSv/MBq for women and 1.64×10 mSv/MBq for men., Conclusion: This is the first reported dosimetry of F-FDG in lactating breasts, data that are required when justifying the radiation dose from an F-FDG PET scan in lactating patients. In addition, we calculated more up-to-date EDs from F-FDG that are lower than the current widely reported ED and should be used in future publications on F-FDG.

Objective: Little is known about the effect of maternal handedness and preferential side of breastfeeding upon macronutrients concentration in human milk (HM). We aimed to compare macronutrients content of HM from both breasts, taking into account the self-reported preferential feeding ('dominant') breast, breast size and handedness (right versus left). We tested the null hypothesis that macronutrients content of HM is not affected by breast dominancy, breast size or maternal handedness., Study Design: Fifty-seven lactating mothers were recruited. HM macronutrients were measured after mid manual expression using infrared transmission spectroscopy., Results: Out of the 57 mothers recruited, 12 were excluded from the analyses because they brought in insufficient samples. Among the 22 who reported a size difference, 16 (73%) had a larger left breast (P<0.001). Approximately a third of women reported no breastfeeding side dominance, a third reported a right dominance and another third reported a left dominance. Breastfeeding side dominance was unaffected by either handedness or breasts size. When size asymmetry was reported (n=22) the dominant side was also the larger breast in 16 (73%) women, the smaller breast in 2 (9%) women, whereas 4 (18%) additional women with asymmetry had no preferential breastfeeding side. There were no statistically significant differences in macronutrients between the right and the left breasts. In multiple stepwise backward regression analysis, fat, carbohydrate, protein and energy contents were unaffected by maternal handedness, breast side dominance or breast size asymmetry., Conclusions: Macronutrients content of mid expression HM is unaffected by maternal handedness, breast size or breast side dominance.

Lactation is the most extreme case of normal physiological bone loss during a lifetime, and breast cancers have a strong tendency to metastasize to bone. In both the physiological and pathological circumstances, parathyroid hormone-related peptide (PTHrP) plays a central role. Until recently there were no regulatory mechanisms to explain the induction of endocrine PTHrP secretion from breast cells during lactation. The mammary epithelium possesses a local serotonin signaling system which drives PTHrP expression during lactation and in breast cancer cells. The mammary gland serotonin system is highly induced in response to alveolar dilation due to milk secretion. Discovery of serotonergic control of PTHrP suggests that it may be possible to manipulate the breast-to-bone axis by targeting serotonin signaling., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

The pregnancy-lactation cycle (PLC) is a period in which the breast is transformed from a less-developed, nonfunctional organ into a mature, milk-producing gland that has evolved to meet the nutritional, developmental, and immune protection needs of the newborn. Cessation of lactation initiates a process whereby the breast reverts to a resting state until the next pregnancy. Changes during this period permanently alter the morphology and molecular characteristics of the breast (molecular histology) and produce important, yet poorly understood, effects on breast cancer risk. To provide a state-of-the-science summary of this topic, the National Cancer Institute invited a multidisciplinary group of experts to participate in a workshop in Rockville, Maryland, on March 2, 2012. Topics discussed included: 1) the epidemiology of the PLC in relation to breast cancer risk, 2) breast milk as a biospecimen for molecular epidemiological and translational research, and 3) use of animal models to gain mechanistic insights into the effects of the PLC on breast carcinogenesis. This report summarizes conclusions of the workshop, proposes avenues for future research on the PLC and its relationship with breast cancer risk, and identifies opportunities to translate this knowledge to improve breast cancer outcomes.

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide with widespread occurrence in the nervous system and peripheral organs, including the mammary gland. Previously, we have shown that PACAP38 is present in the human milk at higher levels than in respective blood samples. However, it is not known how PACAP levels and the expression of PAC1 receptor change during lactation. Therefore, the aim of our study was to investigate PACAP38-like immunoreactivity (PACAP38-LI) in human colostrums and transitional and mature milk during lactation and to compare the expression of PAC1 receptors in lactating and non-lactating mammary glands. We found that PACAP38-LI was significantly higher in human colostrum samples than in the transitional and mature milk. PACAP38-LI did not show any significant changes within the first 10-month period of lactation, but a significant increase was observed thereafter, up to the examined 17th month. Weak expression of PAC1 receptors was detected in non-lactating sheep and human mammary glands, but a significant increase was observed in the lactating sheep samples. In summary, the present study is the first to show changes of PACAP levels in human milk during lactation. The presence of PACAP in the milk suggests a potential role in the development of newborn, while the increased expressions of PAC1 receptors on lactating breast may indicate a PACAP38/PAC1 interaction in the mammary gland during lactation.

Exclusive breastfeeding is recommended up to 6 months of age, and may be continued in combination with a more diversified diet until 2 years of age. It represents the ideal natural diet for the newborn. The current change of maternity care policy and the adherence to the Baby Friendly Hospital Initiative (BFHI) project, have been associated with a significant improvement of patient information. This positive aspect combined with the effect of perinatal education were major contributors for breastfeeding promotion. This article presents the physiology of breastfeeding and its practical aspects, useful for the family doctor. The doctor plays a central role both in the information, which might influence the choice of breastfeeding, and also in the support of the mother or her baby. The duration of breastfeeding represents the new goal to be emphasized. Lactating mothers should be encouraged to consult competent caregivers, including the family doctor in case of breastfeeding difficulties.

Objective: To investigate the dynamics of milk removal during breast expression., Subjects and Methods: This study used a continuous weighing balance to determine changes in milk flow rate and their relationship to the proportion of milk removed over time and the percentage of the available milk removed during simultaneous expression (15 minutes) of the left and right breasts in 34 mothers of healthy, term, breastfeeding infants., Results: Multiple milk ejections (5.1±2.0; range, two to 14) were detected as increases in milk flow rate. A larger total expression volume was associated with a higher maximum milk flow rate (p<0.001). However, 14% less of the available milk was removed for a 100 g increase in available milk (p<0.001). After 2.9±1.4 and 6.0±2.5 minutes, 50% and 80%, respectively, of the total expression volume was removed. Milk flow was more active in the first 7 minutes than the last 7 minutes. At the eighth minute (midpoint), 54±25% of the available milk and 86±9% of the total expression volume were removed., Conclusions: The maximum milk flow rate was predictive of the total volume expressed. After the eighth minute of expression the milk flow rate was reduced. Increasing volumes of milk in the breast were associated with less complete breast emptying. These data suggest that long expression sessions are not required for mothers who are not pump dependent and that extending intervals between expressions results in less effective milk removal.

The early nursing-sucking relationship is not to be taken for granted in humans. A number of factors can either facilitate or mitigate its optimal establishment on the mother's or newborn's sides. Among these factors, a morphological feature of human mothers' breasts--the areolar glands (AG)--has been identified as potentially important. Three day-old infants display attraction during the presentation of the native secretions of the AG, suggesting that they could influence the newborn's behaviour during breastfeeding. The present study assessed this topic in a sample of 121 Caucasian mother-infant dyads. The areolae of these women were screened during the first 3 postnatal days in parallel with the infant's sucking performance, body weight fluctuations and time to lactation onset. On average, 97% of the women bore AG, 80.2% having 1-20 units per areola and 33% showing AG excreting a visible fluid. The endowment in AG appeared positively linked with neonatal growth after birth and with the speed of lactation onset: infants of primiparous women with lower AG numbers had a lower weight gain than those of mothers with higher AG numbers. Further, it took longer to primiparae with lower AG counts to set on lactation. This study confirms and extends the fact that AG, in interaction with maternal experience, might influence the initiation of the breastfeeding relationship., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Aim: Breastfeeding mothers expressed their breasts hourly for periods up to 7 hours, without exogenous oxytocin, to determine the consistency of milk removal and the relationship between the volume of milk removed and the mother's 24-hour milk production., Methods: Mothers (n = 20) measured their 24-hour milk production from each breast by test-weighing their babies at home. Mothers came to the research laboratory for a day visit and expressed milk from either both or one breast (left or right) for 10-15 minutes, every hour for 2-7 hours. Mothers were not instructed to restrict breastfeeding prior to the first (0-hour) expression., Results: It was found that the milk volume at 1 hour (59.7 +/- 36.5 and 46.5 +/- 25.6 mL/hour for the right and left breast, respectively) was significantly (p < 0.05) higher than the milk volume from subsequent hourly intervals. The average hourly volumes obtained from the 2nd to 7th hour (18.0 +/- 3.1 and 14.0 +/- 4.8 mL/hour for the right and left breast, respectively) were not significantly different from the average hourly rates calculated for the 24-hour milk production (18.4 +/- 6.3 and 15.5 +/- 5.1 mL/hour for the right and left breast, respectively). Furthermore, local inhibition was not observed during hourly expressions of up to 7 hours., Conclusion: The average hourly volumes of milk from the 2nd to 7th hour expressions could provide an estimate of the rate of milk secretion. Further study is required to fully validate these findings.

Maternal obesity is associated with short duration of breastfeeding, and many obese women also have large breasts. To determine if health professionals who support lactating women can distinguish between these maternal characteristics as obstacles to breastfeeding, the authors conducted a mail survey of 242 Danish health professionals. They thought that initiating was more difficult (P < .0001) than continuing breastfeeding for women with large breasts and/or obesity. These difficulties were thought to be lowest for women with large breasts, higher for obese women, and highest for obese women with large breasts (P < .0001). These difficult ratings were significantly related in a complex manner to the respondents' personal characteristics and type of training. These findings indicate the importance of recognizing and treating large breasts and maternal obesity as separate obstacles to successful breastfeeding and that interventions to reduce these obstacles should be designed to account for characteristics of the person providing them.

Mammalian reproduction requires that nursing mothers transfer large amounts of calcium to their offspring through milk. As a result, lactation is associated with dramatic alterations in bone and mineral metabolism, including reversible bone loss. One theme that has emerged from recent studies examining these adaptations is that the lactating breast actively participates in regulating bone and mineral metabolism. This review will detail our current knowledge of interactions between the breast, skeleton, and hypothalamus during lactation and will consider implications that this reproductive physiology has for the pathophysiology of osteoporosis and breast cancer.

On June 20, 1947 a meeting at the Royal Society of Medicine in London was entitled "Discussion on Some Recent Developments in Knowledge of the Physiology of the Breast". The major questions outlined by the speakers were: how does the structure of the breast change with reproductive stage? What is the role of the basal cell layer in the mammary epithelium? How is milk composition related to diet? And what is the basic physiology of milk secretion including its hormonal regulation? All these questions were attacked vigorously in laboratories mostly in England and the United States, but researchers in France, Germany, and Austria also weighed in. Our purpose in this edition of the Journal is to show, through the presentation of seminal papers and key references, how the research of that period, prior to the molecular revolution of the last three decades, laid the groundwork for our current understanding of the morphology, developmental biology, and physiology of the functional mammary gland. This knowledge provides the groundwork for our current research into the molecular mechanisms involved in milk secretion and its regulation.

Mouse mammary gland involution resembles a wound healing response with suppressed inflammation. Wound healing and inflammation are also associated with tumour development, and a 'wound-healing' gene expression signature can predict metastasis formation and survival. Recent studies have shown that an involuting mammary gland stroma can promote metastasis. It could therefore be hypothesised that gene expression signatures from an involuting mouse mammary gland may provide new insights into the physiological pathways that promote breast cancer progression. Indeed, using the HOPACH clustering method, the human orthologues of genes that were differentially regulated at day 3 of mammary gland involution and showed prolonged expression throughout the first 4 days of involution distinguished breast cancers in the NKI 295 breast cancer dataset with low and high metastatic activity. Most strikingly, genes associated with copper ion homeostasis and with HIF-1 promoter binding sites were the most over-represented, linking this signature to hypoxia. Further, six out of the ten mRNAs with strongest up-regulation in cancers with poor survival code for secreted factors, identifying potential candidates that may be involved in stromal/matrix-enhanced metastasis formation/breast cancer development. This method therefore identified biological processes that occur during mammary gland involution, which may be critical in promoting breast cancer metastasis that could form a basis for future investigation, and supports a role for copper in breast cancer development.

Cysteine cathepsins are proteolytic enzymes that reside in endolysosomal vesicles. Some are expressed constitutively while others are transcriptionally regulated. However, the expression and subcellular localization of cathepsins changes during cancer progression and cathepsins have been shown to be causally involved in various aspects of tumorigenesis including metastasis. The use of mouse models of breast cancer genetically ablated for cathepsin B has shown that both the growth of the primary tumor and the extend of lung metastasis is reduced by the loss of cathepsin B. The role of cathepsins in involution of the mammary gland has received little attention although it is clear that cathepsins are involved in tissue remodeling in the second phase of involution. We discuss here the roles of cathepsins and their endogenous inhibitors in breast tumorigenesis and post-lactational involution.

Postlactational involution is the process following weaning during which the mammary gland undergoes massive cell death and tissue remodeling as it returns to the pre-pregnant state. Lobular involution is the process by which the breast epithelial tissue is gradually lost with aging of the mammary gland. While postlactational involution and lobular involution are distinct processes, recent studies have indicated that both are related to breast cancer development. Experiments using a variety of rodent models, as well as observations in human populations, suggest that deregulation of postlactational involution may act to facilitate tumor formation. By contrast, new human studies show that completion of lobular involution protects against subsequent breast cancer incidence.

Background and Objective: Mechanical characteristics of breast pumps have been shown to influence milk extraction and hormone release in laboratory settings. However, few studies evaluate impact of differences in pump design on long-term breastfeeding success. This study evaluated the impact of a novel pump design on milk extraction, milk fat content, maternal hormone response, maternal satisfaction, long-term milk production, and duration of breastfeeding following return to the workforce., Design and Methods: Healthy women intending to return to work or school and to breastfeed exclusively for

The purpose of the present study was to measure changes in blood volume and the oxygenation state of breast tissue during breastfeeding with the use of near-infrared time-resolved spectroscopy (TRS) as a noninvasive method. Forty breastfeeding mothers were divided into 2 groups in which measurements were made in the contralateral breast (group A) and in the ipsilateral breast (group B). The tissue concentrations of oxyhemoglobin, deoxyhemoglobin, and total hemoglobin and the hemoglobin oxygen saturation were measured in the breast by using TRS during a breastfeed. In both groups A and B, the values of all parameters decreased significantly after the start of breastfeeding compared with the pre-breastfeeding values. The values of all parameters fluctuated cyclically after the beginning of the breastfeed. Time-resolved spectroscopy is an effective noninvasive method for investigating the hemodynamics of the breast during breastfeeding.

Although it is well recognized that a thorough understanding of the anatomy of an organ is essential to enable assessment of any abnormalities in that organ, there has been little investigation of the anatomy of the normal lactating breast since Sir Astley Cooper performed detailed dissections of the anatomy of the breast more than 160 years ago. Many mothers recognize that breast milk provides the ultimate nutrition and protection for the infant; however, a significant proportion of women experience difficulties breastfeeding, some of which lead to weaning the infant. Recently, a small number of studies have focused on the gross anatomy of the breast, and have found that the ductal system is comprised of fewer numbers of main ducts than previously thought. In addition, the ducts are compressible and do not contain large amounts of milk, the amount of fatty tissue in the breast is variable, and a proportion is situated within the glandular tissue. These findings add to our understanding of both the physiology and pathology of the lactating breast.

This article reports the naturally occurring pattern of milk output beginning day 6 through day 42 postpartum from each individual breast in 95 pump-dependent mothers of a non-nursing preterm infant. Of the 3488 study days, milk output was greater from the left breast on 51.6% (n = 1800) of the study days, from the right breast 45.8% (n = 1598) of the study days, and equal 2.6% (n = 90) of the study days. Overall, total left and right breast milk output for the entire study (37 days) was 52.6% and 47.4%, respectively. There was no significant relationship between individual breast milk output and maternal handedness, parity, or breastfeeding experience. Clinicians need to assess the total milk output as well as individual breast output in lactating mothers, as there may be significant disparities in milk production.

Purpose: Milk output from the right and left breasts was compared in mothers who were pumping exclusively and had not yet fed their infants at breast., Methods: Thirty-five mothers of very low birthweight infants established lactation with a hospital grade, electric, dual pump, and recorded milk output separately for each breast during every pumping session from enrollment until completion of the study (mean = 19.8 days) using a standardized milk log. Milk output from each breast was also weighed during six observed milk expressions over a 2-week period during the study., Results: For the observed pumping sessions (n = 210), milk output was greater from the right breast in 65.7% of the sessions. For the milk log data (n = 3099 pumping sessions) milk output was greater from the right breast in 47.6% of the sessions, greater from the left breast in 28.0%, and equal from both breasts in 24.4% of the sessions. The mean difference in milk output between the right and left breasts was 6.6 mL (SD = 12.1) for the observed sessions, and 5.0 mL for the milk log data (SD = 10.9). The mean right-to-left breastmilk output ratio was 1.20 for the observed sessions and 1.17 for the milk log data. The right-to-left breastmilk ratios were not associated with time of day, day of pumping, total milk output, maternal handedness or the breast pump suction pattern. The right-to-left breast differences were associated with parity and breastfeeding experience, with primiparous women and first-time breastfeeders demonstrating the greatest differences., Conclusions: These findings suggest that differences in the milk output from the right and left breasts are common, and that milk output is often greater from the right breast. The differences appear early in lactation, are not related to total milk output, and are relatively consistent throughout the day and over the first weeks of lactation.

My research into the physiology of lactation began at the University of Sydney in the early 1960s with funding from the Australian Dairy Industry. In 1972 I moved to The University of Western Australia to teach medical students and initiated a research program in human lactation. Coincidentally this was a very significant time for human lactation because 1972 was the nadir for breastfeeding in many Western countries, including Australia. In Western Australia the proportion of women choosing to breastfeed increased from <50% to the current rate of approximately 95%. Because the invasive conventional techniques used to study lactation in laboratory and domestic animals could not be applied to investigation of the regulation of milk synthesis in lactating women, it was necessary to develop new approaches to the study of mammary gland metabolism in women. These methods have included measuring breast volume using a computerized breast measurement system, measuring milk macro- and micro-components on small volumes of breast milk, bioluminescent metabolomic assays, and ultrasound analysis of breast function. Currently, my research is directed toward understanding the control of synthesis, secretion, and removal of milk in women with the aim of developing clinical protocols for the assessment of the normal and abnormal function of the lactating breast.

Objective: The objective was to investigate changes in milk composition that reflect variations in breast permeability, milk synthesis, and immune response in women before, during, and after mastitis., Methods: Mothers (n = 26) were followed prospectively from day 5 postpartum to the end of their lactation. Milk from each breast, blood, 24-hour urine samples, and data on breast and systemic pathologies were collected at reference intervals during the first 3 months postpartum, daily during the occurrence of any breast inflammation, and 7 days after resolution of symptoms, and was analyzed using mixed-model analysis (repeated measures)., Results: There was a significant difference in sodium (p < 0.001), chloride (p < 0.001), serum albumin (p < 0.02) and lactose (p < 0.003) in the breast with mastitis when compared with both the contralateral asymptomatic breast and "healthy" breasts. Inflammation of the whole breast was a significant predictor for a decreased glucose (p < 0.01) and hyperacute systemic symptoms predicted a decrease in milk glucose (p < 0.03) and an increased lactoferrin (p < 0.05) and sIgA (p < 0.03)., Conclusions: There is an increased breast permeability, reduced milk synthesis, and increased concentration of the immune components sIgA and lactoferrin with increasing severity of breast and systemic symptoms. The changes observed in milk composition during periods of increased breast permeability cannot be solely explained by the current theory of permeability of the paracellular pathway and further research in this area is required.

Currently there is no simple method available to assess milk ejection and breast milk flow in lactating women in both the clinical and research setting. The authors hypothesize that changes in milk flow rate are associated with milk ejection and therefore may provide a method suitable for the assessment of milk ejection and removal. Mothers (n = 23) expressed milk from one breast for a 15-minute period using both weak and strong vacuums on two to four separate occasions using an experimental electric breast pump (Medela AG, Baar, Switzerland). Breast milk flow rates were recorded at 5-second intervals by connecting a tube from the breast shield to a bottle placed on a balance that was connected to a computer. Milk ejection was determined by an acute increase in milk duct diameter in the contralateral breast using ultrasound (Acuson XP10, Siemens, Mountain View, CA), and the change in duct diameter was compared with milk flow rates. Milk flow rates ranged from 0 to 4.6 g per 5-second period. Increases in flow rates were positively associated with increases in duct diameter (p < 0.05). Furthermore, within each milk ejection, higher maximum duct diameters were positively related to greater volumes expressed per 5-second periods (p < 0.001). Time to the first milk ejection and number of milk ejections were the same when determined by ultrasound or flow rates. This direct relationship between increases in duct diameter and acute increases in milk flow rates suggests that changes in flow rates can be used to identify milk ejection in the absence of ultrasound data.

This study aimed to use ultrasound imaging to investigate the milk ejection characteristics of women during a 10-minute expression using an electric breast pump capable of applying 2 markedly different vacuum patterns. The classic pattern (47 cycles/min) and 3-phase pattern (pre-milk ejection: 120 cycles/min, post-milk ejection: 20 cycles/min for 2 minutes post-milk ejection then 55-78 cycles/min for 8 minutes) were tested, and the milk expressed was collected in 30-second intervals. Multiple milk ejections (96%) were detected (classic: 3.27+/-2.05; 3-phase: 3.72+/-1.19) and associated with increases in milk flow. Almost half of the total volume of milk expressed was removed during the first milk ejection (classic: 41.38+/-21.48%; 3-phase: 46.72+/-26.60%). There was no correlation between the number of milk ejections and both the total volume of milk and percentage of available milk for either pattern. In conclusion, milk ejection characteristics and efficiency of milk expression did not change in response to different expression patterns.

A retrospective study was undertaken to evaluate the ability of breast-feeding using lateral pedicle reduction mammaplasty. A standard questionnaire was sent to 72 patients who had been operated on at a fertile age. Data was collected regarding the duration and quality of preoperative and postoperative breast-feeding, difficulties while breast-feeding, reasons for discontinuation of breast-feeding or for not attempting to breast-feed, and postoperative subjective sensitivity. Thirteen of the women who replied to the questionnaire had given birth after surgery. The pressure threshold sensitivity of areola-nipple complex was measured in nine of the above cases. To preserve lactation, a technique leaving structures untouched within the pedicle with increased dimensions was used.Breast-feeding was considered successful in this study if it was performed exclusively, without supplementation, for two months. Seven women (54%) breast-fed successfully for between two and 14 months (5.8+/-1.3) following surgery. Two women (16%) were classified as unsuccessful and four women (30%) did not breast-feed at all. The success of breast-feeding was limited by nonsurgical factors including the influence of medical personal. Five of eight women (62%) who had children preoperatively improved their rate of breast-feeding after surgery. No correlation was demonstrated between measured sensitivity and breast-feeding (p=0.65). No significant correlation was found between the resected tissue and breast-feeding (p=0.08). No relation was observed between the duration of breast-feeding and the period between operation and partus.

Objective: To investigate the difference in breast symptoms between breast binding and support bra wearing in nonbreastfeeding postpartum mothers., Design: A systematic replication of an earlier study by Bristol using a pre-experimental posttest design., Setting: A private, for-profit hospital in a city in the south-central region of the United States., Participants: Sixty nonbreastfeeding postpartum women who gave birth to viable newborns of singleton gestations, had an uncomplicated postpartum, and did not receive hormonal lactation suppressants., Main Outcome Measures: Postpartum breast engorgement, leakage, tenderness, and use of pain relief measures as measured by the Bristol Record of Symptoms., Results: Analysis of the data revealed no significant difference relative to breast engorgement between the two groups during the first 10 postpartum days. However, the breast-binder group reported a greater degree of breast tenderness, breast leakage, and use of other pain relief measures., Conclusion: Breast binding should be discontinued as a method of lactation suppression and use of support bras encouraged. Future studies need to focus on comfort for nonbreastfeeding, postpartum mothers.

To test the effect on milk ejection, an electric breast pump was programmed to provide pumping patterns with frequencies of 45 to 125 cycles/min and vacuums of 45 to -273 mm Hg. The time taken for milk ejection to occur (measured using ultrasound to detect a dilation of a lactiferous duct in the opposite breast) in response to the current Medela electric breast pump pattern (45 cycles/min) was 147 +/- 13 s. For patterns that more closely resemble the sucking frequency of an infant when it first attaches to the breast, milk ejection occurred between 136 +/- 12 and 104 +/- 10 s, although this difference was not statistically significant. Milk ejection in response to breastfeeding occurred after 56 +/- 4 s. The applied vacuum affected the amount of milk that was removed up to 50 to 70 s after milk ejection but not the time for milk ejection.